ABSTRACT
The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior.
Subject(s)
Amphetamine/pharmacology , Central Nervous System Stimulants/pharmacology , Central Nervous System/metabolism , Dopamine/metabolism , Social Behavior , Analysis of Variance , Animals , Animals, Newborn , Anxiety/pathology , Arvicolinae , Body Weight/drug effects , Body Weight/physiology , Central Nervous System/drug effects , Disease Models, Animal , Dopamine/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Locomotion/drug effects , Male , Maze Learning/drug effects , Maze Learning/physiology , RNA, Messenger/metabolism , Receptors, Dopamine/genetics , Receptors, Dopamine/metabolism , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolismABSTRACT
Sleep deprivation is common place in modern society. Nowadays, people tend to self-impose less sleep in order to achieve professional or social goals. In the social context, late-night parties are frequently associated with higher availability of recreational drugs with abuse potential. Physiologically, all of these drugs induce an increase in dopamine release in the mesolimbic dopaminergic system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems to play an important role in the events related to the neurotransmission of the dopaminergic system by potentiating its behavioral effects. In this scenario, the aim of the present study was to investigate the effects of total sleep deprivation (6h) on the acute cocaine-induced locomotor stimulation in male mice. Animals were sleep deprived or maintained in their home cages and subsequently treated with an acute i.p. injection of 15mg/kg cocaine or saline and observed in the open field. Total sleep deprivation for 6h potentiated the hyperlocomotion induced by acute cocaine administration. In addition, the cocaine sleep deprived group showed a decreased ratio central/total locomotion compared to the cocaine control group, which might be related to an increase in the impulsiveness of mice. Our data indicate that acute periods of sleep loss should be considered risk factors for cocaine abuse.
Subject(s)
Central Nervous System Stimulants/pharmacology , Cocaine/pharmacology , Hyperkinesis/chemically induced , Sleep Deprivation/psychology , Animals , Hyperkinesis/psychology , Male , MiceABSTRACT
Persistence of a drug-environment conditioning induced by repeated psychostimulant treatment is thought to play a key role in the addictive cycle. In addition, sleep disorders are a common feature in patients with addictive disorders. Sleep deprivation shares similar neurobiological effects with psychostimulants. Therefore, we investigated whether sleep deprivation would impair the extinction of previously established conditioning between the drug effect and the environmental cues. Four cohorts of male adult mice underwent a behavioral sensitization procedure pairing drug (cocaine at 15 mg/kg, i.p.) or saline with environment (open-field apparatus). The extinction of conditioned locomotion was evaluated after control (home-cage maintained) or sleep deprivation (gentle handling method for 6h) conditions. Sleep deprivation both postponed the initiation and impaired the completeness of extinction of the conditioned locomotion promoted by previous drug-environment conditioning in cocaine-sensitized animals. While the cocaine control group required 5 free-drug sessions of exposure to the open-field apparatus to complete extinction of conditioned locomotion, the cocaine pre-treated group that experienced sleep deprivation before each extinction session still significantly differed from its respective control group on Day 5 of extinction. The possibility that the sleep condition can influence the extinction of a long-lasting association between drug effects and environmental cues can represent new outcomes for clinically relevant phenomena.
Subject(s)
Cocaine/administration & dosage , Conditioning, Operant , Sleep Deprivation/physiopathology , Animals , Male , MiceABSTRACT
The effect of home cage conspecifics' behavior on locomotor sensitization to amphetamine (AMP) or ethanol (ETOH) were investigated. Female mice were repeatedly treated with saline or AMP (2.0 mg/kg for 13 days--Experiment 1) or saline or ETOH (1.8 g/kg for 21 days--Experiment 2) in home cages where all the animals had the same treatment (homogeneous home cages--HOM-HC) or in home cages where half of the animals were drug-treated and half of them were saline-treated (heterogeneous home cages--HET-HC). Behavioral sensitization was evaluated by the quantification of open-field locomotor activity after AMP or ETOH challenge injection, respectively. In both experiments, behavioral sensitization was potentiated in HOM-HC maintained animals. These results suggest that the behavioral sensitization phenomenon can be modified by home cage conspecifics' behavior.
Subject(s)
Amphetamine/pharmacology , Behavior, Animal/drug effects , Ethanol/pharmacology , Analysis of Variance , Animals , Female , MiceABSTRACT
The studies on the relationship between the light/dark cycle and memory function mostly used protocols of acute disruption of the circadian rhythm. The aim of the present study is to verify the effects of long-term continuous exposure to light on memory, anxiety and motor parameters of mice tested in the plus-maze discriminative avoidance task. Mice were conditioned to choose between the two enclosed arms (one aversive and one non-aversive) while avoiding the open arms of a modified elevated plus-maze apparatus. Memory was evaluated by the time spent in the aversive enclosed arm, anxiety was evaluated by the time spent in the open arms and locomotor behavior was evaluated by number of entries in the arms of the maze. The results showed that long-term (35-42 days) continuous light exposure did not modify memory or anxiety parameters but increased locomotor activity. While the increase in locomotor behavior is in line with previous studies, the unexpected absence of alterations in memory and anxiety (reported to be influenced by the circadian rhythm) is discussed.
