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1.
Psychiatry Res ; 218(3): 335-40, 2014 Aug 30.
Article in English | MEDLINE | ID: mdl-24844977

ABSTRACT

Drug-induced behavioral sensitization (BS), paradoxical sleep deprivation (PSD) and adolescence in rodents are associated with changes in the mesolimbic dopaminergic system. We compared the effects of PSD on amphetamine-induced BS in adult and adolescent mice. Adult (90 days old) and adolescent (45 days old) Swiss mice were subjected to PSD for 48h. Immediately after PSD, mice received saline or 2.0mg/kg amphetamine intraperitoneally (i.p.), and their locomotion was quantified in activity chambers. Seven days later, all the animals were challenged with 2.0mg/kg amphetamine i.p., and their locomotion was quantified again. Acute amphetamine enhanced locomotion in both adult and adolescent mice, but BS was observed only in adolescent mice. Immediately after its termination, PSD decreased locomotion of both saline- and amphetamine-treated adolescent mice. Seven days later, previous PSD potentiated both the acute stimulatory effect of amphetamine and its sensitization in adolescent mice. In adult animals, previous PSD revealed BS. Our data suggest that adolescent mice are more vulnerable to both the immediate and long-term effects of PSD on amphetamine-induced locomotion. Because drug-induced BS in rodents shares neuroplastic changes with drug craving in humans, our findings also suggest that both adolescence and PSD could facilitate craving-related mechanisms in amphetamine abuse.


Subject(s)
Behavior, Animal/physiology , Central Nervous System Stimulants/pharmacology , Sleep Deprivation/physiopathology , Sleep, REM/physiology , Age Factors , Amphetamine , Amphetamine-Related Disorders/physiopathology , Animals , Behavior, Animal/drug effects , Disease Models, Animal , Locomotion/drug effects , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Motor Activity/physiology , Sleep, REM/drug effects
2.
Clin Exp Pharmacol Physiol ; 41(3): 255-63, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24471703

ABSTRACT

1. It has been suggested that the high prevalence of drug abuse in schizophrenics is related to chronic treatment with typical neuroleptics and dopaminergic supersensitivity that develops as a consequence. Within this context, atypical neuroleptics do not seem to induce this phenomenon. In the present study, we investigated the effects of acute administration or withdrawal from long-term administration of haloperidol and/or ziprasidone on morphine-induced open-field behaviour in mice. 2. In the first experiment, mice were given a single injection of haloperidol (1 mg/kg, i.p.) or several doses of ziprasidone (2, 4 or 6 mg/kg, i.p.) and motor activity was quantified by the open-field test. The aim of the second experiment was to verify the effects of an acute injection of haloperidol (1 mg/kg) or ziprasidone (6 mg/kg) on 20 mg/kg morphine-induced behaviours in the open-field test. In the third experiment, mice were treated with 1 mg/kg haloperidol and/or 2, 4 or 6 mg/kg ziprasidone for 20 days. Seventy-two hours after the last injection, mice were injected with 20 mg/kg, i.p., morphine and then subjected to the open-field test. Acute haloperidol or ziprasidone decreased spontaneous general activity and abolished morphine-induced locomotor stimulation. 3. Withdrawal from haloperidol or ziprasidone did not modify morphine-elicited behaviours in the open-field test. The results suggest that withdrawal from neuroleptic treatments does not contribute to the acute effect of morphine in schizophrenic patients.


Subject(s)
Antipsychotic Agents/pharmacology , Behavior, Animal/drug effects , Morphine/pharmacology , Animals , Female , Haloperidol/pharmacology , Mice , Motor Activity/drug effects , Piperazines/pharmacology , Substance Withdrawal Syndrome/drug therapy , Thiazoles/pharmacology
3.
Psychiatry Res ; 208(1): 74-7, 2013 Jun 30.
Article in English | MEDLINE | ID: mdl-23618352

ABSTRACT

We investigated whether the effect of neonatal hypoxia on amphetamine-induced hyperlocomotion can reproduce the ontogenic (age of onset) properties of schizophrenia. Neonatal hypoxia enhanced amphetamine-induced hyperlocomotion in adult mice and decreased it in adolescent mice. These findings provide ontogenic validity for this very simple animal model of schizophrenia.


Subject(s)
Dextroamphetamine/pharmacology , Hyperkinesis/chemically induced , Hypoxia/psychology , Schizophrenia/chemically induced , Age Factors , Animals , Animals, Newborn , Disease Models, Animal , Male , Mice
4.
Alcohol Clin Exp Res ; 37 Suppl 1: E30-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22827480

ABSTRACT

BACKGROUND: A considerable amount of experimental evidence has demonstrated ethanol (EtOH) induced amnestic effects following EtOH administration during pretraining in a variety of tasks both in humans and in laboratory animals. Although the phenomenon of state-dependency is known to play a critical role in memory deficits induced by both pharmacological and nonpharmacological pretraining perturbations, the involvement of this phenomenon in EtOH-induced anterograde amnesia has been overlooked. This study aimed to investigate the role of state-dependency in EtOH-induced amnestic effects and its interactions with the well-known anxiolysis and locomotor alterations. METHODS: Mice were treated with 1.2 or 2.4 g/kg EtOH before training and/or before testing in the plus-maze discriminative avoidance task, an animal model that concomitantly evaluates learning, memory, anxiety-like behavior, and general activity. RESULTS: Whereas both doses of EtOH induced anxiolysis, the 1.2 g/kg dose enhanced locomotion while the 2.4 g/kg dose decreased it. In addition, the administration of 1.2 g/kg of this drug during pretraining caused memory impairment, which was counteracted by the pretest administration of the same dose, revealing the participation of the state-dependency. Conversely, the administration of 2.4 g/kg EtOH led to amnestic effects irrespective of the time of the administration (pretraining and/or pretest), eliminating the influence of state-dependency. CONCLUSIONS: Our data demonstrate that EtOH-induced memory deficits are critically related to state-dependency, which can also be affected by the dose range. These results indicate the possible participation of EtOH-induced modifications in anxiety and motor activity levels in relation to state-dependent memory deficits.


Subject(s)
Avoidance Learning/drug effects , Discrimination Learning/drug effects , Ethanol/toxicity , Memory Disorders/chemically induced , Animals , Avoidance Learning/physiology , Discrimination Learning/physiology , Dose-Response Relationship, Drug , Male , Memory Disorders/physiopathology , Mice , Random Allocation
5.
Addict Biol ; 16(4): 565-79, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21790900

ABSTRACT

Repeated or even a single exposure to drugs of abuse can lead to persistent locomotor sensitization, which is the result of an abundance of neuroplastic changes occurring within the circuitry involved in motivational behavior and is thought to play a key role in certain aspects of drug addiction. There is substantial controversy about the addictive potential of modafinil, a wake-promoting drug used to treat narcolepsy that is increasingly being used as a cognitive enhancer and has been proposed as a pharmacotherapy for cocaine dependence. Male mice were used to investigate the ability of modafinil to induce locomotor sensitization after repeated or single administration in mice. Bidirectional cross-sensitization with cocaine and modafinil-induced conditioned place preference were also evaluated. Both repeated and single exposure to moderate and high doses of modafinil produced a pronounced locomotor sensitization that cross-sensitized in a bidirectional way with cocaine. Remarkably, when cocaine and modafinil were repeatedly administered sequentially, their behavioral sensitization was additive. Supporting these behavioral sensitization data, modafinil produced a pronounced conditioned place preference in the mouse. Taken together, the present findings provide pre-clinical evidence for the addictive potential of modafinil. Our data also strongly suggest that similar neural substrates are involved in the psychomotor/rewarding effects of modafinil and cocaine.


Subject(s)
Benzhydryl Compounds/pharmacology , Central Nervous System Sensitization/drug effects , Central Nervous System Sensitization/physiology , Central Nervous System Stimulants/pharmacology , Cocaine-Related Disorders/physiopathology , Cocaine/pharmacology , Motor Activity/drug effects , Motor Activity/physiology , Neuronal Plasticity/drug effects , Neuronal Plasticity/physiology , Substance-Related Disorders/physiopathology , Animals , Brain/drug effects , Brain/physiopathology , Choice Behavior/drug effects , Choice Behavior/physiology , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Dose-Response Relationship, Drug , Drug Synergism , Injections, Intraperitoneal , Male , Mice , Modafinil , Motivation/drug effects , Motivation/physiology , Reward , Social Environment
6.
Drug Alcohol Depend ; 118(2-3): 349-59, 2011 Nov 01.
Article in English | MEDLINE | ID: mdl-21596493

ABSTRACT

BACKGROUND: Behavioral sensitization in rodents is hypothesized to reflect neuronal adaptations that are related to drug addiction in humans. We evaluated the effects of group exposure on the acute hyperlocomotion and behavioral sensitization induced by four drugs of abuse in C57BL/6 mice: methylenedioxymethamphetamine (MDMA), d-amphetamine, morphine and ethanol. METHODS: In the priming session, animals received an ip injection of one of the drugs of abuse and were exposed to an open field either individually or in groups of four. Seven days later, we assessed behavioral sensitization in the challenge session. All animals received an ip injection of the same drug and were exposed to the open field in the same social conditions described for the priming session. Locomotion and social interaction were quantified during each session. RESULTS: Acute MDMA, morphine and ethanol, but not d-amphetamine, increased social interaction. However, group exposure only potentiated MDMA-induced hyperlocomotion. After a challenge injection of each drug, there was no sensitization to the facilitating effect of MDMA, morphine or ethanol on social interaction, but locomotion sensitization developed to all drugs of abuse except ethanol. This sensitization was potentiated by group exposure in MDMA-treated animals, attenuated in morphine-treated animals and not modified in d-amphetamine-treated animals. Acute MDMA enhanced body contact and peaceful following, while acute morphine and ethanol increased social sniffing. CONCLUSIONS: These results provide preclinical evidence showing that while different drugs of abuse affect different components of social interaction, the neuronal adaptations related to drug dependence can be critically and specifically influenced by group exposure.


Subject(s)
Behavior, Animal/drug effects , Hyperkinesis/chemically induced , Motor Activity/drug effects , Social Behavior , Animals , Central Nervous System Sensitization/drug effects , Central Nervous System Stimulants/pharmacology , Dextroamphetamine/pharmacology , Ethanol/pharmacology , Injections , Male , Mice , Morphine/pharmacology , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Narcotics/pharmacology
7.
Pharmacol Biochem Behav ; 98(2): 320-4, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21277887

ABSTRACT

Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intraperitoneal injection of saline or amphetamine (1.0, 2.0 or 4.0 mg/kg). Seven days later, half of the mice from the saline group received a second injection of saline. The remaining animals were challenged with 2.0 mg/kg amphetamine. Following all of the injections, mice were placed in activity chambers and locomotion was quantified for 45 min. The magnitude of both the acute and sensitized locomotor stimulatory effect of amphetamine was higher in the adolescent mice. Previous experience with the test environment inhibited the acute amphetamine stimulation in both adolescent and adult mice, but facilitated the detection of elevated spontaneous locomotion in adolescent animals. These results support the notion that the adolescent period is associated with an increased risk for development of drug abuse. Additionally, they indicate a complex interaction between the environmental novelty, adolescence and amphetamine.


Subject(s)
Amphetamine-Related Disorders/etiology , Amphetamine-Related Disorders/psychology , Amphetamine/administration & dosage , Behavior, Animal/drug effects , Behavior, Animal/physiology , Sexual Maturation/physiology , Adolescent , Adult , Animals , Behavior, Addictive/physiopathology , Behavior, Addictive/psychology , Disease Models, Animal , Humans , Injections, Intraperitoneal , Male , Mice , Motor Activity/drug effects , Motor Activity/physiology
8.
Sleep ; 33(12): 1669-79, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21120129

ABSTRACT

STUDY OBJECTIVES: A considerable amount of experimental evidence suggests that sleep plays a critical role in learning/memory processes. In addition to paradoxical sleep, slow wave sleep is also reported to be involved in the consolidation process of memories. Additionally, sleep deprivation can induce other behavioral modifications, such as emotionality and alternations in locomotor activity in rodents. These sleep deprivation-induced alterations in the behavioral state of animals could produce state-dependent learning and contribute, at least in part, to the amnestic effects of sleep deprivation. The aim of the present study was to examine the participation of state-dependent learning during memory impairment induced by either paradoxical sleep deprivation (PSD) or total sleep deprivation (TSD) in mice submitted to the plus-maze discriminative avoidance or to the passive avoidance task. DESIGN: Paradoxical sleep deprivation (by the multiple platform method) and total sleep deprivation (by the gentle handling method) were applied to animals before training and/or testing. CONCLUSIONS: Whereas pre-training or pre-test PSD impaired retrieval in both memory models, pre-training plus pre-test PSD counteracted this impairment. For TSD, pre-training, pre-test, and pre-training plus pre-test TSD impaired retrieval in both models. Our data demonstrate that PSD- (but not TSD-) memory deficits are critically related to state-dependent learning.


Subject(s)
Learning/physiology , Memory Disorders/etiology , Memory Disorders/psychology , Sleep Deprivation/psychology , Animals , Anxiety , Behavior, Animal , Disease Models, Animal , Male , Memory Disorders/physiopathology , Mice , Motor Activity/physiology , Sleep Deprivation/physiopathology , Stress, Psychological/complications , Stress, Psychological/physiopathology , Stress, Psychological/psychology
9.
Prog Neuropsychopharmacol Biol Psychiatry ; 31(1): 65-70, 2007 Jan 30.
Article in English | MEDLINE | ID: mdl-16876303

ABSTRACT

Numerous studies have described memory deficits following sleep deprivation. There is also evidence that the absence of sleep increases brain oxidative stress. The present study investigates the effects of a pro-oxidant agent--3-nitropropionic acid (3-NP)--on hippocampal oxidative stress and passive avoidance performance of sleep-deprived mice. Mice were repeatedly treated i.p. with saline or 5 or 15 mg/kg 3-NP and sleep-deprived for 24 h by the multiple platform method--groups of 4-5 animals placed in water tanks, containing 12 platforms (3 cm in diameter) surrounded by water up to 1 cm beneath the surface or kept in their home cage (control groups). The results showed that: (1) neither a 24 h sleep deprivation period nor 3-NP repeated treatment alone were able to induce memory deficits and increased hippocampal lipid peroxidation; (2) this same protocol of sleep deprivation, combined with 15 mg/kg 3-NP repeated treatment, induced memory deficits and an increase in hippocampal lipid peroxidation. The results support the involvement of hippocampal oxidative stress in the memory deficits induced by sleep deprivation and the hypothesis that normal sleep would prevent oxidative stress.


Subject(s)
Hippocampus/metabolism , Lipid Peroxidation/drug effects , Memory/drug effects , Nitro Compounds/pharmacology , Oxidants/pharmacology , Propionates/pharmacology , Sleep Deprivation/metabolism , Sleep Deprivation/psychology , Animals , Avoidance Learning/drug effects , Hippocampus/drug effects , Male , Mice
10.
Brain Res ; 1122(1): 179-83, 2006 Nov 29.
Article in English | MEDLINE | ID: mdl-17030027

ABSTRACT

We investigated the effects of reserpine (0.1-0.5 mg/kg) on the performance of mice in the plus-maze discriminative avoidance task (DAVT), which simultaneously evaluates memory and motor activity. All doses induced memory impairment (increased aversive arm time) but only 0.5 mg/kg reserpine decreased locomotion (entries in enclosed arms). The results suggest that the DAVT evaluation in reserpine-treated mice can be a useful model for studying cognitive deficits accompanied by motor impairments.


Subject(s)
Adrenergic Uptake Inhibitors/pharmacology , Avoidance Learning/drug effects , Discrimination Learning/drug effects , Memory Disorders/complications , Parkinsonian Disorders/complications , Reserpine/pharmacology , Analysis of Variance , Animals , Disease Models, Animal , Dose-Response Relationship, Drug , Male , Maze Learning/drug effects , Memory Disorders/chemically induced , Mice , Motor Activity/drug effects , Parkinsonian Disorders/chemically induced
11.
Pharmacol Biochem Behav ; 81(4): 923-7, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16083952

ABSTRACT

A biphasic effect of morphine on locomotion has been extensively described. Nevertheless, the effects of this opioid on other behavioral parameters have been overlooked. The aim of the present study was to verify the effects of different doses of morphine on motor behaviors observed in an open-field. Adult female mice were injected with saline or morphine (10, 15 and 20 mg/kg, i.p.) and observed in an open-field for quantification of locomotor and rearing frequencies as well as duration of immobility and grooming. The lowest dose of morphine decreased locomotion (and increased immobility duration) while the highest dose increased it. All doses tested decreased rearing and grooming. Thus, the effects of morphine on locomotion do not parallel to its effects on rearing and grooming. Our results indicate that locomotion not always reflects the effect of drugs on motor activity, which can be better investigated when other behavioral parameters are concomitantly taken into account.


Subject(s)
Behavior, Animal/drug effects , Morphine/pharmacology , Motor Activity/drug effects , Analgesics, Opioid/pharmacology , Animals , Dose-Response Relationship, Drug , Female , Grooming/drug effects , Mice
12.
Psychopharmacology (Berl) ; 176(2): 115-22, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15160262

ABSTRACT

RATIONALE: Several clinical studies demonstrate that the absence of periods of sleep is closely related to occurrence of anxiety symptoms. However, the basis of these interactions is poorly understood. Studies performed with animal models of sleep deprivation and anxiety would be helpful in the understanding of the mechanisms underlying this relationship, but some animal studies have not corroborated clinical data, reporting anxiolytic effects of sleep deprivation. OBJECTIVES: The aim of the present study was to verify the effects of different protocols of sleep deprivation in mice tested in the elevated plus-maze and to assess the effect of chlordiazepoxide and clonidine. METHODS: Three-month-old male mice were sleep-deprived for 24 or 72 h using the methods of single or multiple platforms in water tanks. Mice kept in their home cages were used as controls. Plus-maze behavior was observed immediately after the deprivation period. RESULTS: Mice that were sleep-deprived for 72 h spent a lower percent time in the open arms of the apparatus than control animals. This sleep deprivation-induced anxiety-like behavior was unaffected by treatment with chlordiazepoxide (5.0 and 7.5 mg/kg IP), but reversed by an administration of 5 or 10 microg/kg IP clonidine. CONCLUSION: The results indicate that under specific methodological conditions sleep deprivation causes an increase in anxiety-like behavior in mice exposed to the elevated plus-maze.


Subject(s)
Anxiety/psychology , Maze Learning/physiology , Sleep Deprivation/psychology , Animals , Anxiety/drug therapy , Chlordiazepoxide/pharmacology , Chlordiazepoxide/therapeutic use , Clonidine/pharmacology , Clonidine/therapeutic use , Dose-Response Relationship, Drug , Male , Maze Learning/drug effects , Mice , Sleep Deprivation/drug therapy
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