Unilateral electrical stimulation of the inferior colliculus of rats modifies the prepulse modulation of the startle response (PPI): effects of ketamine and diazepam.

The magnitude of an acoustic startle response can be reduced by a weak stimulus presented immediately before the startle-eliciting noise. This phenomenon has been termed prepulse inhibition of the startle reaction (PPI). Previous studies indicated that the primary neural pathways mediating PPI belong to the brain stem and that the inferior colliculus (IC) was crucial. Its destruction reduced PPI. Stimulations applied to brain areas may be as deleterious as lesions. Therefore, we looked for the possibility of a brain stimulation applied to the IC during a PPI test to reduce also PPI. Rats were implanted with chronic electrodes, their tips being aimed at the IC. They were located within or close to the inter-colliculus nucleus. A train of stimulations was applied and PPI was tested alternately during and between periods of stimulation. As the most common method used to attenuate PPI consists in administrating drugs, for example ketamine, we also tested the effect of this drug. Another drug was also tested, diazepam, since it alters the functioning of the IC without any known effect on PPI. This allowed a comparative analysis of the neurobiological and the pharmacological effects. It appeared that the stimulation decreased PPI quantitatively as much as ketamine (6 mg/kg) without an effect of the basic startle reaction. These effects did not interfere with each other. Diazepam (1 mg/kg) did not modify PPI, neither under stimulation nor per se. Only for a very high dose (4 mg/kg), a sedative and myo-relaxant one the basic startle and PPI were altered.

[Prenatal manifestation of a congenital glioblastoma - Case report]. / Antepartale sonographische Manifestation eines kongenitalen Glioblastoms.

In prenatal ultrasound screening, internal hydrocephalus and intracranial bleeding of the fetus are considered as primary diagnostic signs for a congenital brain tumor. We report the prenatal sonographic diagnosis of a congenital glioblastoma due to acute fetal internal hydrocephalus in the 37th week of gestation. After birth, the tumor's hyperechoic appearance on ultrasound was indistinguishable from intracranial bleeding. Diagnosis of a congenital glioblastoma (WHO stage IV) was confirmed by subtotal tumorectomy in the 9th week of life. In the international literature, only 6 cases of prenatally diagnosed glioblastomas have so far been reported, all of which associated with sonographically diagnosed fetal hydrocephalus. Further sonographic signs for a brain tumor are the tumor mass itself, a polyhydramnion, enlarged biparietal diameters and head circumferences, as well as suspected intracranial bleeding.

Non-monotonic dependency of PPI on temporal parameters: differential alteration by ketamine and MK-801 as opposed to apomorphine and DOI.

RATIONALE: Prepulse inhibition (PPI) of the startle reflex, a measure of sensorimotor gating, is a time-linked phenomenon which depends on prepulse duration (PD) and prepulse-pulse interval (PP). Rats treated with dopaminergic agonists, serotoninergic agonists or glutamatergic antagonists are commonly used as models for the deficit in PPI observed in schizophrenic patients. An important question was whether there is a parametric specificity for the effects of such pharmacological agents. OBJECTIVE: We investigated the contribution of PD, PP, and then of ratio R (PD:PP) to the expression of PPI and we looked for a modification of the temporal dependency of PPI by either apomorphine, DOI, ketamine and/or MK-801. METHODS: Male Sprague-Dawley rats were used. The values used to test PD varied from 5 to 1280 ms, with PP being fixed at 20 ms and vice versa to test PP. Different ratios were used to test R. The effect of either apomorphine (0.5 mg/kg), DOI (1 mg/kg), ketamine (1.5-6 mg/kg) or MK-801 (0.1-0.5 mg/kg) was compared to their vehicle. RESULTS: PPI was a non-monotonic function of each parameter tested. The functions of PD and PP differed. All drugs reduced PPI in each parameter. The shape of the function obtained by varying PD was modified by ketamine and MK-801, but not by apomorphine or DOI. CONCLUSIONS: The specific effect of ketamine and MK-801 was discussed in relation to the hypotheses about the mechanism underlying the modulation of PPI by temporal parameters. These findings stress the importance of non-competitive NMDA antagonist-induced disruption of PPI as a model of the sensorimotor gating deficit observed in schizophrenic patients.

Differential effect of free intake versus oral perfusion of sucrose in conditioned taste aversion in rats.

Five experiments were designed to investigate LiCl-induced conditioned taste aversion (CTA) obtained in rats whether after free intake of a sucrose solution (active mode) or after forced administration through an intraoral cannula (passive mode). It was found in Experiment 1 that actively conditioned rats showed a slower extinction rate as revealed by repeated two-bottle tests (active testing) as opposed to passively conditioned ones. As these rats underwent a mode change between conditioning and testing, the differential extinction rate might have arisen from this change inducing a generalization decrement effect or acting as a contextual shift. In Experiment 2, no evidence for any generalization decrement was found. The possibility that the mode of sucrose delivery could have contextual properties in CTA through a "renewal test" after extinction and a latent inhibition experiment was further tested in Experiments 3 and 4. When active testing followed passive extinction, a CTA was afresh obtained in rats actively conditioned in active conditions. Latent inhibition was attenuated in rats preexposed in passive conditions and conditioned in active conditions (i.e., when a shift in the drinking mode occurred between preexposure and conditioning). In Experiment 5, intraoral perfusion was used in both groups. The active subjects had to nose poke for intraoral administration of sucrose. The yoked control passive subjects received simultaneously the same amount of sucrose. The levels of CTA differed also from the actively to the passively conditioned subjects. Results are discussed in terms of free intake activity acting as a contextual modulator of CTA.

Associative learning and latent inhibition in a conditioned suppression paradigm in humans.

A paradigm based on conditioned suppression of ongoing motor activity, sensitive to latent inhibition (LI), was developed and tested in healthy volunteers. Subjects were trained to move disks from one peg to another with a high degree of regularity in the Tower of Toronto puzzle, a well-known cognitive skill learning task. Once this was achieved, they were submitted to a Pavlovian conditioning procedure. The conditioned stimulus (CS) was a pure tone and the unconditioned stimulus (US) a loud white noise. The resulting response suppression was assessed by a transient increase in latency of the hand movements. In control subjects, there was non-contingent CS and US presentation. The results evidenced conditioning after a single CS-US pairing. Following five preexposures to the to-be-conditioned CS, however, conditioning was abolished, seemingly expressing LI. Because a weak unconditioned response to the tone was observed after its first two presentations, an additional experiment was performed with two preexposures to the to-be-conditioned CS. With such procedure, conditioning was obtained, supporting the existence of LI in the preceding experiment. These results indicate that the present paradigm may be useful for the study of LI in human subjects, having the advantage of being similar to the experimental conditions used in the majority of LI studies in experimental animals.

Reduction of latent inhibition by D-amphetamine in a conditioned suppression paradigm in humans.

The sensitivity of latent inhibition (LI) to amphetamine has been tested in humans with a paradigm close to the conditioned emotional response suppression currently used in experimental animals. The conditioned stimulus (CS) was a tone, the unconditioned stimulus (US) a strong white noise, and the response a transient delay in a regular sequence of hand movements in the resolution of the Tower of Toronto puzzle. The aim of this study was to verify whether the previously reported, disruptive effect of CS preexposure on conditioning really represents LI, by examining its sensitivity to amphetamine. Three groups of healthy volunteers received placebo, 5 or 10 mg of dexamphetamine sulphate, respectively, in a double-blind experimental design. The preexposure, conditioning and test phases were carried out under either amphetamine or placebo. The non preexposed groups treated with amphetamine were not different from the non preexposed placebo group, indicating that amphetamine did not affect conditioning. Among the preexposed groups, those receiving 10 mg of amphetamine showed normal rates of conditioning, whereas those treated with either 5 mg of amphetamine or placebo showed LI. Similar results have been reported in experimental animals. This sensitivity to amphetamine suggests that the present paradigm may be used to study LI in humans.

A neurotoxic lesion of serotonergic neurones using 5,7-dihydroxytryptamine does not disrupt latent inhibition in paradigms sensitive to low doses of amphetamine.

Testing the effects of low doses of d-amphetamine on latent inhibition (LI) in two different conditioning paradigms, passive avoidance and conditioned taste aversion, provided evidence of their pharmacological equivalence. For passive avoidance, LI was expressed by the decreased latency to enter a shock compartment in preexposed rats placed 5 min in the compartment during 3 consecutive days before conditioning. In the conditioned taste aversion paradigm, a group of rats was preexposed to a solution of sucrose also for 3 consecutive days prior to the establishment of an association between sucrose and sickness elicited by an injection of LiCl. On the following day, the preexposed rats drunk more sucrose when allowed to choose between one tube containing water and an other containing sucrose. In both paradigms, 0.25 mg/kg d-amphetamine, injected daily on the 3 preexposure days and on the conditioning day, decreased LI. A dose of 0.5 mg/kg suppressed LI in the passive avoidance paradigm. The effect of a serotonergic lesion induced by i.c.v. injection of 5,7-dihydroxytryptamine (5,7-DHT) was evaluated in the same paradigms. The lesion procedure that lowered hippocampal serotonin and 5 HIAA levels by more than 80% did not affect LI. Taken together, the present results lessens the hypothesis that LI is prone to an opposing influence of the two monoaminergic systems considered in this work.

Myoclonic and tonic seizures elicited by microinjection of cholinergic drugs into the inferior colliculus.

The inferior colliculus (IC) is the initiation site in the neuronal network for the epileptic audiogenic seizure (AGS). The present study investigates the effects of alteration of IC cholinergic transmission on the elicitation of epileptic seizures. Unilateral microinjections of carbachol (3 and 6 micrograms/0.2 microliter) into the IC elicited intense locomotor activity, contraversive rotations and myoclonic seizures. This result indicates that the IC is the initiation site for the induction of myoclonic seizures and suggests that these myoclonic seizures may result from activation of m1 muscarinic receptors. Microinjections of the nicotinic-muscarinic antagonist, gallamine (2 and 6 micrograms/0.2 microliter), into the IC induced AGS susceptibility. However, microinjections of muscarinic antagonists, atropine (15 micrograms/0.2 microliter) and scopolamine (12 and 20 micrograms/0.2 microliter), or the nicotinic antagonist, hexamethonium (12 and 20 micrograms/0.2 microliter), into the IC have no effect. Gallamine-induced AGS susceptibility may result from a selective blockade of m2 muscarinic receptors.

Cognitive skill learning and schizophrenia: implications for cognitive remediation.

The ability to acquire a motor and cognitive skill was investigated in 26 patients with schizophrenia and 26 normal participants using repeated testing on the Tower of Toronto puzzle. Seven patients with defective performance were retested using additional trials and immediate feedback designed to facilitate problem solving. A component analysis of performance was used based on J. R. Anderson's (1987) model of cognitive skill learning. Patients exhibited a performance deficit on both motor and cognitive skills. However, their acquisition rate was similar to that of normal participants on most parameters, indicating that skill learning suffered little or no impairment. Performance deficit was accounted for by poor problem-solving ability, explicit memory, and general intellectual capacities. It was remediable in some, but not all, patients. Remediation failure was also related to severe defects of cognitive functions.

Signaled two-way avoidance learning using electrical stimulation of the inferior colliculus as negative reinforcement: effects of visual and auditory cues as warning stimuli.

The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colliculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 +/- 6.15 (A, peak-to-peak) was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 +/- 0.60 s and 8.63 +/- 0.93 s for latencies and 12.5 +/- 2.04 and 19.62 +/- 1.65 for frequencies in the first and second halves of the sessions, respectively, P < 0.01 in both cases). No significant changes in latencies (14.75 +/- 1.63 and 12.75 +/- 1.44 s) or frequencies of responses (8.75 +/- 1.20 and 11.25 +/- 1.13) were seen when tone was used as the warning stimulus (P > 0.05 in both cases). Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala.

The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil.

The effects of gamma-hydroxybutyrate (GHB), a product of gamma-aminobutyric acid (GABA) metabolism which possesses neuromodulatory properties in brain, were investigated in the elevated plus maze in rats. The number of entries and the time spent in the open arms of the maze were increased by GHB (50, 150, 250 mg/kg i.p.). This is classically considered as indicative of an anxiolytic effect of the drug. There was no sedative effect at these doses as measured by the spontaneous locomotor activity in the actimeter or the total number of arm entries. The anxiolytic properties of GHB were reversed by neither the GHB receptor antagonist, NCS-382 (6,7,8,9-tetrahydro-5(H)-5-olylidene acetic acid) (300 mg/kg i.p.), nor the opioid receptor antagonist, naloxone (10 mg/kg i.p.). However the anti-anxiety effect of GHB was antagonized by the benzodiazepine receptor antagonist, flumazenil (10 mg/kg i.p.), suggesting an interaction of GHB with the GABA(A) receptor complex which mediates the anti-anxiety effect of benzodiazepines.

Signaled two-way avoidance learning using eletrical stimulation of the inferior colliculus as negative reinforcement: effects of visual and auditory cues as warning stimuli

The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colluculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance pardigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 + 6.15 (A, peak-to-peak) was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 + 0.60 s and 8.63 + 0.93 for lactencies and 12.5 + 2.04 and 19.62 + 1.65 frequencies in the first and second halves of the sessions, respectively, P<0.01 in both cases). No significant changes in latencies (14.75 + 1.63 and 12.75 + 1.44 s) or frequencies of responses (8.75 + 1.20 and 11.25 + 1.13) were seen when tone was used as the warning stimulus (P>0.05 in both cases). Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala.

Bilateral ablation of the auditory cortex in the rat alters conditioned emotional suppression to a sound as appraised through a latent inhibition study.

Latent inhibition consists of a retardation of conditioning seen when the to be conditioned stimulus is presented a number of times with no other consequence. This phenomenon likely reflects processes of selective attention whereby irrelevant stimuli come to be ignored. Using physiological models for auditory attention, some investigators have suggested that selective attention acts as a filtering mechanism capable of inhibiting or gating unattended stimuli relative to attended ones in the auditory cortex. In the present work, an on-baseline conditioned suppression response procedure was used to study the effects of stimulus preexposure in rats submitted to bilateral auditory cortex ablation. Our results indicate that both auditory cortex lesioned and control animals exhibit latent inhibition to a sound. However, learning after preexposure to that sound was particularly slow in animals with bilateral auditory cortex lesion, i.e. in these animals, the latent inhibition effect appeared to be enhanced. Conditioning from one day to the next also varied slightly. Thus, the auditory cortex appears to modulate learning when the conditioned stimulus is a sound.

Effect of midazolam on propofol-induced positive affective state assessed by place conditioning in rats.

BACKGROUND: The effect of either midazolam or the combination of midazolam and propofol on the affective state was assessed in rats at subanesthetic doses and at recovery from anesthesia. METHODS: The putative drug(s)-induced affective states were repeatedly paired with one of two distinguishable compartments of an experimental cage, whereas the vehicle(s)-induced effect was repeatedly paired with the other compartment. During a subsequent choice test for one compartment over the other, the rats' preference for the drug(s)-paired compartment over the vehicle(s)-paired compartment is indicative of a pleasant state induced by the drug(s). In experiment 1, rats were conditioned with different doses of midazolam either at subanesthetic states or at recovery from anesthesia. In experiment 2, groups of rats were conditioned with different combinations of midazolam and propofol either at subanesthetic states or at recovery from anesthesia induced jointly by midazolam (10 mg/kg) and propofol (60 mg/kg). Experiment 3 was conducted in the same way as experiment 2, except that midazolam was paired with both compartments. In addition, these groups were tested not only in an undrugged state but also in a drugged (with midazolam) state. RESULTS: In experiment 1, rats exhibited a place preference for the environment previously associated with midazolam, at subanesthetic and anesthetic doses. Experiment 2 showed that a propofol-induced place preference was found to be dose-dependently suppressed by midazolam. Experiment 3 replicated the findings of experiment 2 and extended them to the mechanism by which midazolam blocked a propofol-induced place preference. CONCLUSIONS: Midazolam administered before propofol blocked the expression of a propofol-induced pleasant state.

Active avoidance learning using brain stimulation applied to the inferior colliculus as negative reinforcement in rats: evidence for latent inhibition.

The inferior colliculus has been implicated in aversive or anxiogenic aspects of defensive behavior. Animals learn to turn off electrical stimulation applied to the inferior colliculus. The purpose of the present study was to determine (1) whether this aversion induced by electrical stimulation can be conditioned to a conditioned stimulus (CS, light) and (2) whether pre-exposure to the CS will diminish the extent of such conditioning, i.e. whether latent inhibition can be established with this paradigm. Rats were placed inside an open field, and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold was used as negative reinforcement and shuttle box illumination as the CS. The rats quickly learned to avoid or terminate the inferior-colliculus stimulation. Furthermore, the performance of the animals in this paradigm was significantly disrupted when they were pre-exposed to 50 presentations of the CS before the session. These data suggest that the inferior colliculus has neural substrates for supporting associative learning and latent inhibition.

Latent inhibition in conditioned emotional response: c-fos immunolabelling evidence for brain areas involved in the rat.

Latent inhibition refers to the fact that the formation of a conditioned association between a conditioned and an unconditioned stimulus is delayed by prior exposure to the conditioned stimulus. Latent inhibition is often investigated in the context of the conditioned emotional response, in which a tone serves as the conditioned and a footshock as the unconditioned stimulus. Such a paradigm was used for the present experiments in which some rats had been pre-exposed to the tone. Two hours after a subsequent exposure to the tone, c-fos immunocytochemistry was used to map activated brain areas. The density of immunoreactive neurones was measured in brain areas involved in audition, fear, stress and memory. For the basic conditioning group, pre-exposure to the tone decreased the density of labelled cells in the auditory system, areas involved in fear and stress and a number of limbic areas, namely the amygdala, the Ammon's horn of the hippocampus and the entorhinal cortex. In contrast, the density increased in three limbic areas: the dentate gyrus, the subiculum and the nucleus accumbens. Taken together, these data suggest that latent inhibition corresponds to alterations of sensory processing which renders difficult to state about the alteration of the transfers of the sensory information to structures involved in the control of emotional responses. As some brain areas show a specific increase of activity in cases of latent inhibition, further studies will investigate how the latter brain areas contribute to the other cell density alterations reported in this study and to the latent inhibition phenomenon itself.

Bicuculline microinjections into the ventral tegmental area of the rat: alteration of self-stimulation thresholds and of cytochrome oxidase activity in the brain.

Abuse of drugs that potentiate GABAergic neurotransmission, namely benzodiazepines, is difficult to understand because this potentiation should elicit, among other effects, a decrease in activity within the mesolimbic system. Abuse of benzodiazepines is difficult to understand since the opposite, namely an increase in mesolimbic activity, has been implicated in drug abuse as well as in the rewarding effect of direct mesolimbic stimulation. In order to evaluate how the activity of the mesolimbic system depends on mesolimbic GABAergic influence, a GABAA receptor antagonist, bicuculline methiodide, was unilaterally injected into the ventral tegmental area and its effect on self-stimulation thresholds derived from stimulations applied to the same area was evaluated. Microinjection of 15, 20 and 30 ng increased the stimulation threshold. This decrease in stimulation efficiency lasted no more than 15 min after which baseline levels were obtained. Such a decrease is paradoxical considering that the manipulation should have released the ventral tegmentum from a tonic inhibitory influence. The metabolic consequences of repeated injections of 30 ng bicuculline were furthermore evaluated by cytochrome oxidase histochemistry. The staining was found to be weak around the injection site and dense in the ipsilateral nucleus accumbens. Release of a tonic GABAergic inhibition added to some cytotoxic damage probably resulted in an increased metabolic activity of this system. The presently reported paradoxical response of the ventral tegmentum and mesolimbic system to a GABAergic challenge may account for the paradoxical relationship between some behavioral properties of the mesolimbic system and GABAergic drugs.

Effect of propofol on affective state as assessed by place conditioning paradigm in rats.

BACKGROUND: Whether propofol produces a pleasant affective state remains unclear from clinical studies. In the current study, the effect on affective state of subanesthetic and anesthetic doses of propofol was assessed at a preclinical level with rats in a place conditioning paradigm. Propofol was compared with methohexital. METHODS: In the place conditioning paradigm, propofol-induced effect was repeatedly paired with one of two distinguishable compartments of the apparatus, whereas the vehicle-induced effect was repeatedly paired with the other compartment. During a subsequent free-choice test, a preference for the drug-paired compartment over the vehicle-paired compartment would be indicative of pleasant state induced by the drug. For all experiments, the conditioning session lasted 8 days and consisted of four pairings of the drug with one compartment and four pairings of the equivalent volume of vehicle with the other compartment. In experiment 1A, four groups of rats were designated according to the dose of propofol that they received intraperitoneally: 0,30,60, or 90 mg/kg. In experiment 1B, the same procedure was used with subanesthetic doses of intraperitoneal methohexital: 0,10,20, or 30 mg/kg. In experiment 2, the rats were conditioned during the recovery period from short-term anesthesia. For one group, anesthesia was induced by propofol (100 mg/kg) whereas for the other group, anesthesia was induced by an equivalent anesthetic dose of methohexital (40 mg/kg). RESULTS: In experiment 1A, the 30-mg/kg, 60-mg/kg, and 90-mg/kg groups showed a place preference for the drug-paired compartment, but only the group conditioned with 60 mg/kg propofol significantly differed from the 0-mg/kg group. In experiment 1B, the groups conditioned with methohexital showed no place preference for the drug-paired compartment. In experiment 2, the rats showed a place preference for the compartment in which they recovered from propofol-induced anesthesia but no place preference for the compartment in which they recovered from methohexital-induced anesthesia. CONCLUSIONS: Propofol, but not methohexital, induced a pleasant affective state in rats at subanesthetic doses as well as during recovery from an anesthetic dose.

Amphetamine-induced conditioned activity does not result from a failure of rats to habituate to novelty.

Psychostimulant-induced conditioned activity is characterized by the presence of a hyperactivity in drug-free rats exposed to an environment previously paired with the effects of a psychostimulant. According to the habituation hypothesis, conditioned activity arises not through a Pavlovian conditioning process but rather because rats under the effects of the psychostimulant would be unable to habituate normally to the environment paired with these effects. This hypothesis predicts that conditioned activity should not develop in a previously habituated environment. This prediction was tested using a within-subject design. In this design, conditioned activity is evidenced when a group of rats, following a vehicle injection, was more active in a previously amphetamine-paired environment than in a previously vehicle-paired environment. The drug-environment pairing involved administering rats with d-amphetamine (1.25 mg/kg; SC) immediately prior to their placement in one of two distinctive environments. On alternate days, the rats received the vehicle and were placed in the other environment. With this design, it was found that: a) conditioned activity developed in a previously habituated environment; b) its magnitude was independent of the number of amphetamine-environment pairings (two, four or eight pairings); c) this development of conditioned activity did not result from a forgetting of the habituated environment due to a state-dependent retention of the habituation. Taken together, these results do not support the habituation hypothesis of psychostimulant-induced conditioned activity.

Neuroanatomical and functional specificity of the basolateral amygdaloid nucleus in taste-potentiated odor aversion.

The present study aimed at documenting the neurobiological substrate of taste-potentiated odor aversion (TPOA) in the rat. The role of several temporal lobe structures in discriminative TPOA learning was questioned. The effects of excitotoxic lesions (ibotenate) of the basolateral amygdaloid nucleus, the central amygdaloid nucleus, the caudate putamen nucleus, and aspirative lesion of the entorhinal cortex were studied. The results show that only basolateral amygdaloid nucleus (ABL) damage impaired TPOA. This effect was selective of TPOA, since it spared conditioned taste aversion (CTA) and olfactory perception. In order to find out which process in TPOA requires normal functioning of the ABL, the effects of microinjections of a GABAA agonist (muscimol) into the ABL at various stages of the experiment were examined. The results show that application of muscimol during the acquisition, before or after the presentation of the odor-taste stimulus, impaired TPOA without affecting CTA. Contrastingly, application of muscimol before the test impaired neither TPOA nor CTA. These results suggest that ABL is involved in the acquisition but not in the retrieval of TPOA. The efficacy of muscimol microinjected after the presentation of the odor-taste stimulus further suggests that the deficit is not due to a sensory impairment but rather to the disruption of a memory process, critical for TPOA.