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1.
Neuroscience ; 404: 153-164, 2019 04 15.
Article in English | MEDLINE | ID: mdl-30742967

ABSTRACT

Adolescent binge drinking renders young drinkers vulnerable to alcohol use disorders in adulthood; therefore, understanding alcohol-induced brain damage and associated cognitive dysfunctions is of paramount importance. Here we investigated the effects of binge-like adolescent intermittent ethanol (AIE) exposure on nonspatial working memory, behavioral flexibility and cholinergic alterations in the nucleus accumbens (NAc) in male and female rats. On postnatal days P25-57 rats were intubated with water or ethanol (at a dose of 5 g/kg) on a 2-day-on/2-day-off cycle and were then tested in adulthood on social recognition and probabilistic reversal learning tasks. During the social recognition task AIE-treated rats spent similar amounts of time interacting with familiar and novel juveniles, indicating an impaired ability to sustain memory of the familiar juvenile. During probabilistic reversal learning, AIE-treated male and female rats showed behavioral inflexibility as indicated by a higher number of trials needed to complete three reversals within a session, longer response latencies for lever selection, and for males, a higher number of errors as compared to water-treated rats. AIE exposure also reduced the number of cholinergic interneurons in the NAc in males and females. These findings indicate AIE-related pathologies of accumbal cholinergic interneurons and long lasting cognitive-behavioral deficits, which may be associated with cortico-striatal hypofunction.


Subject(s)
Cholinergic Neurons/drug effects , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/physiopathology , Ethanol/toxicity , Interneurons/drug effects , Nucleus Accumbens/drug effects , Age Factors , Animals , Cholinergic Neurons/physiology , Cognitive Dysfunction/psychology , Ethanol/administration & dosage , Female , Interneurons/physiology , Male , Memory, Short-Term/drug effects , Memory, Short-Term/physiology , Nucleus Accumbens/physiology , Rats , Rats, Sprague-Dawley
2.
Neurobiol Learn Mem ; 144: 136-146, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28720405

ABSTRACT

While thepsychoactive inhalant toluene causes behavioral effects similarto those produced by other drugs of abuse, the persistent behavioral and anatomical abnormalities induced by toluene exposure are not well known. To mimic human "binge-like" inhalant intoxication, adolescent, male Sprague-Dawley rats were exposed to toluene vapor (5700ppm) twice daily for five consecutive days. These rats remained in their home cages until adulthood (P60), when they were trained in operant boxes to respond to a palatable food reward and then challenged with several different cognitive tasks. Rats that experienced chronic exposure to toluene plus abstinence ("CTA") showed enhanced performance in a strategy set-shifting task using a between-session, but not a within-session test design. CTA also blunted operant and classical conditioning without affecting responding during a progressive ratio task. While CTA rats displayed normal latent inhibition, previous exposure to a non-reinforced cue enhanced extinction of classically conditioned approach behavior of these animals compared to air controls. To determine whether CTA alters the structural plasticity of brain areas involved in set-shifting and appetitive behaviors, we quantified basal dendritic spine morphology in DiI-labeled pyramidal neurons in layer 5 of the medial prefrontal cortex (mPFC) and medium spiny neurons in the nucleus accumbens (NAc). There were no changes in dendritic spine density or subtype in the mPFC of CTA rats while NAc spine density was significantly increased due to an enhanced prevalence of long-thin spines. Together, these findings suggest that the persistent effects of CTA on cognition are related to learning and memory consolidation/recall, but not mPFC-dependent behavioral flexibility.


Subject(s)
Cognition/drug effects , Learning/drug effects , Nucleus Accumbens/drug effects , Prefrontal Cortex/drug effects , Toluene/administration & dosage , Animals , Conditioning, Classical/drug effects , Conditioning, Operant/drug effects , Dendritic Spines/drug effects , Dendritic Spines/pathology , Extinction, Psychological/drug effects , Male , Nucleus Accumbens/pathology , Prefrontal Cortex/pathology , Rats, Sprague-Dawley
3.
J Neuroendocrinol ; 27(10): 772-86, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26258544

ABSTRACT

Gonadotrophin-releasing hormone (GnRH) and gonadotrophin inhibitory hormone (GnIH) are neuropeptides secreted by the hypothalamus that regulate reproduction. GnRH receptors are not only present in the anterior pituitary, but also are abundantly expressed in the hippocampus of rats, suggesting that GnRH regulates hippocampal function. GnIH inhibits pituitary gonadotrophin secretion and is also expressed in the hippocampus of a songbird; its role outside of the reproductive axis is not well established. In the present study, we employed immunohistochemistry to examine three forms of GnRH [mammalian GnRH-I (mGnRH-I), chicken GnRH-II (cGnRH-II) and lamprey GnRH-III (lGnRH-III)] and GnIH in the adult rat hippocampus. No mGnRH-I and cGnRH-II+ cell bodies were present in the hippocampus. Sparse mGnRH-I and cGnRH-II+ fibres were present within the CA1 and CA3 fields of the hippocampus, along the hippocampal fissure, and within the hilus of the dentate gyrus. No lGnRH-III was present in the rodent hippocampus. GnIH-immunoreactivity was present in the hippocampus in cell bodies that resembled astrocytes. Males had more GnIH+ cells in the hilus of the dentate gyrus than females. To confirm the GnIH+ cell body phenotype, we performed double-label immunofluorescence against GnIH, glial fibrillary acidic protein (GFAP) and NeuN. Immunofluorescence revealed that all GnIH+ cell bodies in the hippocampus also contained GFAP, a marker of astrocytes. Taken together, these data suggest that GnRH does not reach GnRH receptors in the rat hippocampus primarily via synaptic release. By contrast, GnIH might be synthesised locally in the rat hippocampus by astrocytes. These data shed light on the sites of action and possible functions of GnRH and GnIH outside of the hypothalamic-pituitary-gonadal axis.


Subject(s)
Astrocytes/metabolism , Gonadotropin-Releasing Hormone/metabolism , Hippocampus/metabolism , Hypothalamic Hormones/physiology , Neurons/metabolism , Animals , Female , Male , Rats, Long-Evans
4.
Behav Brain Res ; 252: 222-9, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23764458

ABSTRACT

The ability to update and modify previously learned behavioral responses in a changing environment is essential for successful utilization of promising opportunities and for coping with adverse events. Valid models of cognitive flexibility that contribute to behavioral flexibility include set-shifting and reversal learning. One immediate effect of acute stress is the selective impairment of performance on higher-order cognitive control tasks mediated by the medial prefrontal cortex (mPFC) but not the hippocampus. Previous studies show that the mPFC is required for set-shifting but not for reversal learning, therefore the aim of the present experiment is to assess whether exposure to acute stress (15 min of mild tail-pinch stress) given immediately before testing on either a set-shifting or reversal learning tasks would impair performance selectively on the set-shifting task. An automated operant chamber-based task, confirmed that exposure to acute stress significantly disrupts set-shifting but has no effect on reversal learning. Rats exposed to an acute stressor require significantly more trials to reach criterion and make significantly more perseverative errors. Thus, these data reveal that an immediate effect of acute stress is to impair mPFC-dependent cognition selectively by disrupting the ability to inhibit the use of a previously relevant cognitive strategy.


Subject(s)
Attention Deficit Disorder with Hyperactivity/etiology , Attention/physiology , Learning Disabilities/etiology , Reversal Learning/physiology , Stress, Psychological/complications , Acute Disease , Analysis of Variance , Animals , Cues , Discrimination, Psychological , Disease Models, Animal , Male , Rats , Rats, Sprague-Dawley , Time Factors
5.
Neuroscience ; 154(3): 877-84, 2008 Jun 26.
Article in English | MEDLINE | ID: mdl-18479836

ABSTRACT

Reinstatement of previously extinguished instrumental responding for drug-related cues has been used as an animal model for relapse of drug abuse, and is differentially affected by inactivation of the core and shell subregions of the nucleus accumbens (NAc). To compare the roles of these subregions in reinstatement induced by cues associated with natural and drug rewards, the present study assessed the effects of inactivation of the NAc core and shell on cue-induced reinstatement of food-seeking behavior. Rats acquired a lever pressing response for food reward paired with a light/tone conditioned stimulus (CS). They were then subjected to extinction, where both food and the CS were withheld. Reinstatement of responding was measured during response-contingent presentations of the CS. Following saline infusions into the NAc core or shell, rats displayed a significant increase in lever pressing during reinstatement sessions. Inactivation of the core, induced by infusion of GABA agonists muscimol and baclofen, attenuated responding for the CS, but did not affect pavlovian approach toward the food receptacle. In contrast, inactivation of the shell had the opposite effect, potentiating responding relative to vehicle treatments. These data suggest that the NAc core and shell play opposing, yet complementary roles in mediating the influence that food-associated conditioned stimuli exert over behavior. The core enables reward-related stimuli to bias the direction and vigor of instrumental responding. In contrast, the shell facilitates alterations in behavior in response to changes in the incentive value of conditioned stimuli. The fact that the NAc core appears to play a similar role in cue-induced reinstatement induced by both natural and drug rewards suggests that this region of the ventral striatum may be a final common pathway through which both drug- and food-associated stimuli may influence the direction and magnitude of ongoing behavior.


Subject(s)
Conditioning, Operant/physiology , Cues , Feeding Behavior/physiology , Nucleus Accumbens/physiology , Animals , Baclofen/administration & dosage , Baclofen/pharmacology , Conditioning, Operant/drug effects , Data Interpretation, Statistical , Extinction, Psychological/physiology , Feeding Behavior/drug effects , Food , GABA Agonists/administration & dosage , GABA Agonists/pharmacology , Male , Microinjections , Motor Activity/drug effects , Muscimol/administration & dosage , Muscimol/pharmacology , Rats , Rats, Long-Evans
6.
Neuroscience ; 146(4): 1484-94, 2007 Jun 08.
Article in English | MEDLINE | ID: mdl-17449185

ABSTRACT

Reinstatement of previously extinguished instrumental responding for drug-related cues has been used as an animal model for relapse of drug abuse, and is disrupted by inactivation of the basolateral amygdala (BLA). However, the role that the BLA plays in reinstatement induced by cues associated with natural rewards is unclear. The present study assessed the effects of inactivation of different regions of the BLA in cue-induced reinstatement of food-seeking behavior and in the extinction of instrumental responding for food. In experiment 1, rats acquired a lever pressing response for food reward paired with a light/tone conditioned stimulus (CS). They were then subjected to extinction training, where both food and the CS were withheld. Reinstatement of extinguished responding was measured during response-contingent presentations of the CS alone. Following saline infusions into the caudal or rostral BLA, rats displayed a significant increase in lever pressing during reinstatement sessions. Inactivation of these subregions with bupivacaine did not attenuate responding for the CS in the absence of food delivery. In fact, inactivation of the caudal BLA potentiated responding relative to vehicle treatments. Analysis of within-session responding revealed that caudal BLA inactivation retarded extinction of lever pressing in response to the CS. In experiment 2, inactivation of the caudal BLA on the first or second day of extinction training significantly retarded the acquisition of extinction learning on the following day. These data indicate that that the caudal BLA may play a specific role in the extinction of appetitive conditioned responses, by monitoring changes in the reinforcing value of pavlovian conditioned stimuli linked to action-outcome associations once these associations have been formed. Moreover, these findings support a growing body of evidence indicating that separate neural circuits incorporating the BLA may play different roles in mediating reinstatement of reward-seeking behaviors induced by either drug or food related stimuli.


Subject(s)
Amygdala/physiology , Conditioning, Psychological , Cues , Extinction, Psychological/physiology , Feeding Behavior/physiology , Reinforcement, Psychology , Acoustic Stimulation , Amygdala/anatomy & histology , Amygdala/drug effects , Analysis of Variance , Anesthetics, Local/pharmacology , Animals , Behavior, Animal , Bupivacaine/pharmacology , Male , Rats , Rats, Long-Evans , Time Factors
7.
Behav Brain Res ; 126(1-2): 115-26, 2001 Nov 29.
Article in English | MEDLINE | ID: mdl-11704257

ABSTRACT

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex-hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 microg of estradiol benzoate or sesame oil vehicle approximately 4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.


Subject(s)
Association Learning/drug effects , Choice Behavior/drug effects , Conditioning, Operant/drug effects , Estradiol/analogs & derivatives , Estradiol/pharmacology , Maze Learning/drug effects , Mental Recall/drug effects , Retention, Psychology/drug effects , Amygdala/drug effects , Animals , Brain Mapping , Corpus Striatum/drug effects , Dose-Response Relationship, Drug , Female , Hippocampus/drug effects , Neuronal Plasticity/drug effects , Prefrontal Cortex/drug effects , Rats , Rats, Long-Evans
8.
Behav Neurosci ; 115(4): 934-9, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11508732

ABSTRACT

Dopamine (DA) in the medial prefrontal cortex (PFC) can modulate the short-term retention of information and other executive functions. The present study examined whether administration of a DA D1 agonist into the PFC could have differential effects on memory retrieval in circumstances in which memory was either excellent or poor. Separate groups of rats were trained on a delayed version of the radial maze task. On the test day, the delay between the phases was either 30 min or 12 hr. Infusions of the D1 receptor agonist SKF 81297 (0.05, 0.10, or 0.20 microg/0.5 microl) into the PFC before the test phase improved memory retrieval after a 12-hr delay but disrupted performance after a 30-min delay. These data suggest that D1 receptor activity can exert differential effects over PFC function, depending on the strength of the memory trace. When memory is decremented by an extended delay, activation of PFC DA D1 receptors by an agonist can improve cognitive function.


Subject(s)
Dopamine Agonists/pharmacology , Dopamine/metabolism , Maze Learning/drug effects , Memory, Short-Term/physiology , Prefrontal Cortex/drug effects , Animals , Benzazepines/pharmacology , Cognition/drug effects , Maze Learning/physiology , Memory, Short-Term/drug effects , Prefrontal Cortex/metabolism , Rats , Rats, Long-Evans
9.
J Neurosci ; 21(16): 6370-6, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11487660

ABSTRACT

Interactions between the basolateral amygdala (BLA) and the nucleus accumbens (NAc) mediate reward-related processes that are modulated by mesoaccumbens dopamine (DA) transmission. The present in vivo electrophysiological study assessed: (1) changes in the firing probability of submaximal BLA-evoked single neuronal firing activity in the NAc after tetanic stimulation of the BLA, and (2) the functional roles of DA and NMDA receptors in these processes. Tetanic stimulation of the BLA potentiated BLA-evoked firing activity of NAc neurons for a short duration ( approximately 25 min). This short-term potentiation was associated with an increase in DA oxidation currents that was monitored with chronoamperometry. Systemic or iontophoretic application before BLA tetanus of the D(1) receptor antagonist SCH23390, but not the D(2) receptor antagonist sulpiride, abolished the potentiation of BLA-evoked NAc activity, whereas administration of SCH23390 3 min after tetanus had no effect. However, systemic administration of the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), either before or after BLA tetanus, abolished the potentiation of BLA-evoked firing of NAc neurons. These data suggest that higher-frequency activity in BLA efferents can autoregulate their excitatory influence over neural activity of NAc neurons by facilitating the release of DA and activating both DA D(1) and NMDA receptors. This may represent a cellular mechanism that facilitates approach behaviors directed toward reward-related stimuli that are mediated by BLA-NAc circuitries.


Subject(s)
Amygdala/metabolism , Neurons/metabolism , Nucleus Accumbens/metabolism , Receptors, Dopamine D1/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Dopamine/metabolism , Dopamine Antagonists/pharmacology , Electric Stimulation , Electrochemistry , Electrodes, Implanted , Excitatory Amino Acid Antagonists/pharmacology , Iontophoresis , Male , Nucleus Accumbens/cytology , Rats , Rats, Long-Evans , Receptors, Dopamine D1/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Reward
10.
J Neurosci ; 21(13): 4915-22, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11425919

ABSTRACT

Several studies have shown that the mesolimbic dopamine (DA) system is strongly influenced by the ventral subiculum (vSub) of the hippocampus. To examine whether this occurs by activation of DA neuron firing, the effects of chemical stimulation of the vSub on ventral tegmental area (VTA) DA neuron activity were examined using extracellular single-unit recordings. Infusions of NMDA into the vSub increased the number of spontaneously firing DA cells recorded per electrode track, while having no effect on firing rate or burst firing. This response was abolished by intranucleus accumbens (NAc) infusions of the glutamate receptor antagonist kynurenic acid. This effect did not involve the prefrontal cortex, because infusions of tetrodotoxin into the prefrontal cortex did not affect the increase in spontaneously active DA cells. Infusions of either kynurenic acid into the NAc or tetrodotoxin into the vSub decreased the firing rate and burst firing of DA neurons without altering the number of spontaneously active DA neurons. These data show that glutamatergic afferents from the vSub to the NAc exert a potent excitatory effect on VTA DA neurons, influencing both DA neuron population activity and the regulation of the firing properties of these neurons. As a result, dysfunctions in hippocampal circuitries may contribute to the hyperexcitable state of the DA system that is present in schizophrenia.


Subject(s)
Glutamic Acid/metabolism , Hippocampus/physiology , Neurons/metabolism , Nucleus Accumbens/metabolism , Ventral Tegmental Area/metabolism , Action Potentials/drug effects , Action Potentials/physiology , Afferent Pathways/physiology , Animals , Cell Count , Dopamine/metabolism , Dose-Response Relationship, Drug , Hippocampus/cytology , Hippocampus/drug effects , Kynurenic Acid/administration & dosage , Male , N-Methylaspartate/administration & dosage , Neurons/cytology , Neurons/drug effects , Nucleus Accumbens/cytology , Nucleus Accumbens/drug effects , Prefrontal Cortex/cytology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Rats , Rats, Sprague-Dawley , Tetrodotoxin/administration & dosage , Ventral Tegmental Area/cytology
11.
J Neurosci ; 21(8): 2851-60, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11306637

ABSTRACT

Inputs from multiple sites in the telencephalon, including the hippocampus and basolateral amygdala (BLA), converge on neurons in the nucleus accumbens (NAc), and dopamine (DA) is believed to play an essential role in the amplification and gating of these different limbic inputs. The present study used extracellular single-unit recordings of NAc neurons in combination with chronoamperometric sampling of mesoaccumbens DA efflux to assess the importance of DA in the integration of different limbic inputs to the NAc. Tetanic stimulation of the fimbria potentiated hippocampal-evoked firing activity of NAc neurons and increased DA extracellular levels. Systemic administration of the D(1) receptor antagonist SCH23390 or the NMDA receptor antagonist CPP abolished the potentiation of hippocampal-evoked activity and produced a D(2) receptor-mediated suppression of evoked firing. In neurons that received converging input from the hippocampus and BLA, fimbria tetanus potentiated hippocampal-evoked firing activity and suppressed BLA-evoked activity in the same neurons. Both D(1) and NMDA receptors participated in the potentiation of fimbria-evoked activity, whereas the suppression of BLA-evoked activity was blocked by either D(1) receptor antagonism with SCH23390 or the adenosine A(1) antagonist 8-cyclopentyl-1,2-dimethylxanthine. Coincidental tetanus of both the fimbria and BLA resulted in potentiation of both inputs, indicating that DA and adenosine-mediated suppression of BLA-evoked firing was activity-dependent. These data suggest that increases in mesoaccumbens DA efflux by hippocampal afferents to the NAc play a critical role in an input selection mechanism, which can ensure preferential responding to the information conveyed from the hippocampus to the ventral striatum.


Subject(s)
Amygdala/physiology , Dopamine/metabolism , Hippocampus/physiology , Neurons/metabolism , Nucleus Accumbens/metabolism , Action Potentials/drug effects , Action Potentials/physiology , Animals , Dopamine/pharmacology , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Electric Stimulation , Excitatory Amino Acid Antagonists/pharmacology , Fornix, Brain/physiology , Glutamic Acid/metabolism , Male , Nerve Net/metabolism , Neurons/drug effects , Nucleus Accumbens/cytology , Nucleus Accumbens/drug effects , Purinergic P1 Receptor Antagonists , Rats , Rats, Long-Evans , Reaction Time/drug effects , Reaction Time/physiology , Receptors, Dopamine D1/antagonists & inhibitors , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
12.
Psychopharmacology (Berl) ; 151(2-3): 242-51, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10972471

ABSTRACT

RATIONALE AND OBJECTIVES: The role of glutamatergic afferents from the hippocampus in the modulation of dopamine (DA) efflux in the nucleus accumbens (NAcc) and concomitant increases in locomotor activity was examined following brief high-frequency electrical stimulation of the ventral subiculum (vSub). Reverse dialysis of ionotropic glutamate receptor (iGluR) antagonists into the NAcc identified the relative contributions of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the modulation of DA efflux, whereas microinjection of these compounds or selective DA D1 or D2 receptor antagonists were used to analyze the roles of glutamatergic and DA receptors in the stimulation-induced hyperlocomotion. METHODS AND RESULTS: Electrical stimulation of the vSub at 20 Hz (10 s, 300 microA) induced a significant increase in (1) DA levels in the NAcc (approximately 30% from pre-stimulation DA levels) and (2) locomotor activity (approximately 400%). The evoked DA release was completely blocked by reverse dialysis of a selective non-NMDA antagonist DNQX (10 microM and 100 microM), whereas only a high dose of the NMDA antagonist AP-V (100 microM) was effective. The increased motor activity, however, was only slightly attenuated by reverse dialysis of these drugs. Bilateral intra-NAcc injection of DNQX (1 microg/0.5 microl) blocked the increased motor activity induced by vSub stimulation relative to saline treatment. In contrast, bilateral intra-NAcc injection of AP-V (1 microg/0.5 microl) alone caused a significant increase in locomotor activity. The increased motor activity induced by vSub stimulation appears to be mediated through the DA D1 receptor, as systemic administration of the D1 antagonist SCH 23390 (0.25 mg/kg and 1 mg/kg), but not the D2 antagonist sulpiride (2 mg/kg and 10 mg/kg) blocked these effects. CONCLUSIONS: These data indicate an important role for hippocampal glutamatergic afferents in modulating the release of DA through iGluR on DA-receptive neurons in the NAcc and possibly on output neurons to the ventral tegmental area, which subsequently elicits a prolonged increase in locomotor behavior. The role of this circuit in mediating context-dependent behavioral sensitization to repeated administration of psychostimulants is discussed.


Subject(s)
Dopamine/metabolism , Hippocampus/physiology , Motor Activity/physiology , Nucleus Accumbens/physiology , Receptors, Dopamine D1/drug effects , Receptors, Glutamate/drug effects , Animals , Electric Stimulation , Excitatory Amino Acid Antagonists/pharmacology , Extracellular Space/drug effects , Extracellular Space/metabolism , Hippocampus/drug effects , Male , Microdialysis , Nucleus Accumbens/drug effects , Quinoxalines/pharmacology , Rats , Rats, Long-Evans
13.
Neuroreport ; 11(2): 351-4, 2000 Feb 07.
Article in English | MEDLINE | ID: mdl-10674485

ABSTRACT

Rats with cannulae guides implanted in the rhinal cortex were tested on a delayed non-matching-to-sample task, following either lidocaine or sham microinfusions. Bilateral lidocaine microinfusions to the rhinal cortex produced significant delayed non-matching-to-sample deficits. These results are consistent with the putative role of the rhinal cortex in object recognition but because the deficits were not shown to be time dependent, non-mnemonic interpretations cannot be ruled out. These results also illustrate the utility of reversible lidocaine lesions in the study of the neuroanatomical basis of delayed non-matching-to-sample.


Subject(s)
Discrimination Learning , Entorhinal Cortex/physiology , Memory , Reaction Time , Animals , Behavior, Animal/drug effects , Catheterization , Discrimination Learning/drug effects , Entorhinal Cortex/drug effects , Lidocaine/administration & dosage , Male , Memory/drug effects , Microinjections , Rats , Rats, Long-Evans , Reaction Time/drug effects
14.
J Neurosci ; 19(24): 11061-71, 1999 Dec 15.
Article in English | MEDLINE | ID: mdl-10594086

ABSTRACT

The medial dorsal nuclei of the thalamus (MDNt), the prefrontal cortex, and the ventral striatum form an interconnected neural circuit that may subserve certain types of working memory. The present series of experiments investigated functional interactions between these brain regions in rats during the performance of delayed and nondelayed spatially cued radial-arm maze tasks. In Experiment 1, transient inactivation of the MDNt by a bilateral injection of lidocaine selectively disrupted performance on a delayed task but not on a nondelayed random foraging version of the radial arm maze task. In Experiment 2, asymmetrical lidocaine injections into the MDNt on one side of the brain and the prefrontal cortex on the other transiently disconnected these two brain regions and significantly impaired foraging during the delayed task. Similarly, disconnections between the prefrontal cortex and the nucleus accumbens also disrupted foraging on this task, whereas disconnections between the MDNt and the nucleus accumbens had no effect. These data suggest that serial transmission of information among the MDNt, the prefrontal cortex, and the nucleus accumbens is required when trial-unique, short-term spatial memory is used to guide prospective search behavior. The results are discussed with respect to a distributed neural network linking limbic, thalamic, cortical, and striatal regions, which mediates executive functions of working memory.


Subject(s)
Corpus Striatum/physiology , Maze Learning/physiology , Memory/physiology , Prefrontal Cortex/physiology , Thalamic Nuclei/physiology , Anesthetics, Local/pharmacology , Animal Feed , Animals , Corpus Striatum/drug effects , Lidocaine/pharmacology , Male , Neural Pathways/drug effects , Neural Pathways/physiology , Prefrontal Cortex/drug effects , Rats , Rats, Long-Evans , Thalamic Nuclei/drug effects , Time Factors
16.
Eur J Neurosci ; 10(4): 1241-51, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9749778

ABSTRACT

Afferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward-related processes. The present study used in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive-pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time-locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst-patterned stimulation (100 Hz, 5 pulses/burst, 1-s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the nucleus accumbens dose-dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst-patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or gamma-hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward-related stimuli may be mediated, in part, by the basolateral amygdala.


Subject(s)
Amygdala/physiology , Dopamine/metabolism , Nucleus Accumbens/metabolism , Receptors, Glutamate/physiology , Amygdala/drug effects , Anesthetics, Intravenous , Animals , Electric Stimulation , Electrochemistry , Evoked Potentials/drug effects , Evoked Potentials/physiology , Excitatory Amino Acid Antagonists/pharmacology , Male , Nucleus Accumbens/drug effects , Presynaptic Terminals/drug effects , Presynaptic Terminals/metabolism , Rats , Receptors, Glutamate/drug effects , Reward , Stereotaxic Techniques , Urethane
17.
J Neurosci ; 18(4): 1613-21, 1998 Feb 15.
Article in English | MEDLINE | ID: mdl-9454866

ABSTRACT

Dopamine (DA) within the prefrontal cortex (PFC) plays an important role in modulating the short-term retention of information during working memory tasks. In contrast, little is known about the role of DA in modulating other executive aspects of working memory such as the use of short-term memory to guide action. The present study examined the effects of D1 and D2 receptor blockade in the PFC on foraging by rats on a radial arm maze under two task conditions: (1) a delayed task in which spatial information acquired during a training phase was used 30 min later to guide prospective responses, and (2) a nondelayed task that was identical to the test phase of the delayed task but lacked a training phase, thereby depriving rats of previous information about the location of food on the maze. In experiment 1, microinjections of the D1 antagonist SCH-23390 (0.05, 0.5, or 5 microg/µl), but not the D2 antagonist sulpiride (0.05, 0.5, or 5 microg/microl), into the prelimbic region of the PFC before the test phase disrupted performance of the delayed task without affecting response latencies. In contrast, neither drug affected performance of the nondelayed task. In the present study, we also investigated the role of D1 receptors in modulating activity in hippocampal-PFC circuits during delayed responding. Unilateral injections of SCH-23390 into the PFC in the hemisphere contralateral to a microinjection of lidocaine into the hippocampus severely disrupted performance of the delayed task. Thus, the ability to use previously acquired spatial information to guide responding 30 min later on a radial arm maze requires D1 receptor activation in the PFC and D1 receptor modulation of hippocampal inputs to the PFC. These data suggest that D1 receptors in the PFC are involved in working memory processes other than just the short-term active retention of information and also provide direct evidence for DA modulation of limbic-PFC circuits during behavior.


Subject(s)
Hippocampus/physiology , Memory/physiology , Prefrontal Cortex/physiology , Receptors, Dopamine D1/physiology , Space Perception/physiology , Animals , Benzazepines/pharmacology , Child , Dopamine Antagonists/pharmacology , Humans , Injections , Maze Learning/physiology , Neural Pathways/physiology , Prefrontal Cortex/drug effects , Rats , Rats, Inbred Strains , Sulpiride/pharmacology , Time Factors
18.
Eur J Neurosci ; 9(5): 902-11, 1997 May.
Article in English | MEDLINE | ID: mdl-9182943

ABSTRACT

The effects of electrical stimulation of the ventral subiculum/CA1 region of the hippocampus on changes in dopamine oxidation current (corresponding to dopamine efflux) in the nucleus accumbens were examined using in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats. Burst-patterned monophasic pulses (10-100 Hz/burst delivered at 0.8-4 Hz) evoked a three-component change in dopamine efflux in the nucleus accumbens with an initial transient increase in the dopamine signal above baseline, followed by an immediate decrease below baseline, and thereafter by a prolonged increase in the dopamine signal above baseline. 6-Hydroxydopamine lesions of the mesoaccumbens dopamine pathway or transection of the fimbria-fornix blocked all of the evoked changes in the dopamine signal. Both the first and third components of enhanced dopamine efflux were blocked by microinfusion into the nucleus accumbens of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione and kynurenate. Burst stimulation-evoked decreases in the dopamine signal were abolished following microinfusions into the nucleus accumbens of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine. These results suggest that ventral subiculum/CA1 glutamatergic inputs to the nucleus accumbens may presynaptically modulate dopamine efflux by synaptic activation of both ionotropic and metabotropic glutamate receptors in the nucleus accumbens. These glutamate-dopamine interactions may constitute part of the mechanisms by which hippocampal signals are integrated through selective modulation of dopamine release in the nucleus accumbens in both physiological and pathological conditions.


Subject(s)
Dopamine/metabolism , Hippocampus/physiology , Nucleus Accumbens/physiology , Receptors, Glutamate/physiology , Animals , Electric Stimulation , Male , Rats
19.
J Neurosci ; 17(5): 1880-90, 1997 Mar 01.
Article in English | MEDLINE | ID: mdl-9030646

ABSTRACT

The hippocampus, the prefrontal cortex, and the ventral striatum form interconnected neural circuits that may underlie aspects of spatial cognition and memory. In the present series of experiments, we investigated functional interactions between these areas in rats during the performance of delayed and nondelayed spatially cued radial-arm maze tasks. The two-phase delayed task consisted of a training phase that provided rats with information about where food would be located on the maze 30 min later during a test phase. The single-phase nondelayed task was identical to the test phase of the delayed task, but in the absence of a training phase rats lacked previous knowledge of the location of food on the maze. Transient inactivation of the ventral CA1/subiculum (vSub) by a bilateral injection of lidocaine disrupted performance on both tasks. Lidocaine injections into the vSub on one side of the brain and the prefrontal cortex on the other transiently disconnected these two brain regions and significantly impaired foraging during the delayed task but not the nondelayed task. Transient disconnections between the vSub and the nucleus accumbens produced the opposite effect, disrupting foraging during the nondelayed task but not during the delayed task. These data suggest that serial transmission of information between the vSub and the prefrontal cortex is required when trial-unique, short-term memory is used to guide prospective search behavior. In contrast, exploratory goal-directed locomotion in a novel situation not requiring previously acquired information about the location of food is dependent on serial transmission between the hippocampus and the nucleus accumbens. These results indicate that different aspects of spatially mediated behavior are subserved by separate, distributed limbic-cortical-striatal networks.


Subject(s)
Corpus Striatum/physiology , Hippocampus/physiology , Maze Learning/physiology , Prefrontal Cortex/physiology , Afferent Pathways/drug effects , Afferent Pathways/physiology , Anesthetics, Local/pharmacology , Animals , Corpus Striatum/drug effects , Hippocampus/drug effects , Lidocaine/pharmacology , Male , Maze Learning/drug effects , Memory/physiology , Nerve Net/physiology , Nucleus Accumbens/drug effects , Nucleus Accumbens/physiology , Prefrontal Cortex/drug effects , Rats , Spatial Behavior , Time Factors
20.
Behav Neurosci ; 111(6): 1184-96, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9438788

ABSTRACT

Ischemia-induced cell loss in the CA1 region of the dorsal hippocampus results in severe deficits on delayed non-matching-to-sample (DNMS), whereas hippocampectomy produces little or no impairment, suggesting that partial hippocampal damage is more detrimental to DNMS performance than total ablation. To test this hypothesis, rats with or without preoperative DNMS training were given partial cytotoxic lesions of the dorsal hippocampus. When tested, neither group displayed any DNMS deficits despite widespread cell loss in the CA1 and other regions of the dorsal hippocampus. In the final experiments, rats tested previously on DNMS were found to be impaired on the Morris water maze. The finding that partial hippocampal lesions disrupt spatial memory while leaving object-recognition memory intact indicates a specialized role for the hippocampus in mnemonic processes.


Subject(s)
Amnesia/physiopathology , Brain Injuries/physiopathology , Discrimination Learning/drug effects , Hippocampus/drug effects , Maze Learning/drug effects , Pattern Recognition, Visual/drug effects , Temporal Lobe/physiopathology , Animals , Cerebral Cortex/injuries , Cerebral Cortex/pathology , Discrimination Learning/physiology , Disease Models, Animal , Excitatory Amino Acid Agonists , Hippocampus/injuries , Hippocampus/pathology , Hippocampus/physiopathology , Male , Maze Learning/physiology , Memory/drug effects , Memory/physiology , N-Methylaspartate , Orientation/drug effects , Orientation/physiology , Pattern Recognition, Visual/physiology , Rats , Rats, Wistar , Time Factors
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