Reversal learning and experimenter-administered chronic intermittent ethanol exposure in male rats.

Rationale: Chronic alcohol exposure is associated with impaired decision making skills, cognitive deficits, and poor performance on tasks requiring behavioral flexibility. Although oral routes of alcohol administration are commonly used to examine effects of alcohol on various behaviors in rodents, only a few investigations have used intragastric exposures to evaluate ethanol's effects on behavioral flexibility in the adult rat.

Objectives: The aim of the current series of experiments was to determine if behavioral flexibility impairments would be demonstrated across a variety of procedural factors, including route of administration [intraperitoneal injection (i.

Ethanol reduces neuronal excitability of lateral orbitofrontal cortex neurons via a glycine receptor dependent mechanism.

Trauma-induced damage to the orbitofrontal cortex (OFC) often results in behavioral inflexibility and impaired judgment. Human alcoholics exhibit similar cognitive deficits suggesting that OFC neurons are susceptible to alcohol-induced dysfunction. A previous study from this laboratory examined OFC mediated cognitive behaviors in mice and showed that behavioral flexibility during a reversal learning discrimination task was reduced in alcohol-dependent mice.

Cocaine-induced reinstatement of a conditioned place preference in developing rats: involvement of the d2 receptor.

Reinstatement of conditioned place preferences have been used to investigate physiological mechanisms mediating drug-seeking behavior in adolescent and adult rodents; however, it is still unclear how psychostimulant exposure during adolescence affects neuron communication and whether these changes would elicit enhanced drug-seeking behavior later in adulthood. The present study determined whether the effects of intra-ventral tegmental area (VTA) or intra-nucleus accumbens septi (NAcc) dopamine (DA) D2 receptor antagonist infusions would block (or potentiate) cocaine-induced reinstatement of conditioned place preferences. Adolescent rats (postnatal day (PND 28-39)) were trained to express a cocaine place preference.

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice.

In humans, stroke or trauma-induced damage to the orbitofrontal cortex (OFC) or medial prefrontal cortex (mPFC) results in impaired cognitive flexibility. Alcoholics also exhibit similar deficits in cognitive flexibility, suggesting that the OFC and mPFC are susceptible to alcohol-induced dysfunction. The present experiments investigated this issue using an attention set-shifting assay in ethanol dependent adult male C57BL/6J mice.

NR2B-deficient mice are more sensitive to the locomotor stimulant and depressant effects of ethanol.

The NR2B subunit of N-methyl d-aspartate glutamate receptors influences pharmacological properties and confers greater sensitivity to the modulatory effects of ethanol. This study examined behavioral responses to acute ethanol in a conditional knockout mouse model that allowed for a delayed genetic deletion of the NR2B subunit to avoid mouse lethality. Mice lacking the NR2B gene (knockout) were produced by mating NR2B[f/f] mice with CAMKIIa-driven tTA transgenic mice and the tetO-CRE transgenic mice.

Alcohol during adolescence selectively alters immediate and long-term behavior and neurochemistry.

Alcohol use increases across adolescence and is a concern in the United States. In humans, males and females consume different amounts of alcohol depending on the age of initiation, and the long-term consequences of early ethanol consumption are not readily understood. The purpose of our work was to better understand the immediate and long-term impact of ethanol exposure during adolescence and the effects it can have on behavior and dopaminergic responsivity.

Effects of MDMA ("ecstasy") during adolescence on place conditioning and hippocampal neurogenesis.

The use of 3,4,methylenedioxymethamphetamine (MDMA), the active agent in ecstasy, during adolescence is widespread yet the effects on adolescent behavior and brain development are unknown. The aim of the present study was 1) to evaluate effects of MDMA in adolescent rats using the conditioned place preference (CPP) paradigm to measure MDMA-induced reward and 2) assess effects of MDMA administration on cellular proliferation, survival and neurogenesis in the dentate gyrus of the hippocampus. During the adolescent period, MDMA CPP was measured in adolescents [postnatal day (PND) 28-39] by training rats to associate 1.

Localization of stereotaxic coordinates for the ventral tegmental area in early adolescent, mid-adolescent and adult rats.

The ventral tegmental area (VTA) is a brain region implicated in drug addiction and related behaviors; however, little research has been conducted examining the role of the VTA in these processes in adolescent rats. Understanding the development of the VTA is imperative for elucidating mechanisms mediating adolescent vulnerability to drug addiction. The purpose of the present study was to define stereotaxic coordinates for the VTA in developing rats.

Early adolescents show enhanced acute cocaine-induced locomotor activity in comparison to late adolescent and adult rats.

Initiation of drug use during adolescence is associated with an increased probability to develop a drug addiction. The present study examined dose-response effects of cocaine (0, 5, 10, or 20 mg/kg, i.p.

Chronic ethanol exposure during adolescence increases basal dopamine in the nucleus accumbens septi during adulthood.

Background: In humans, adolescent exposure to alcohol is associated with the onset of adult alcohol dependency and suggests that early use potentiates vulnerability to addiction. The aim of the present study was to address whether chronic ethanol exposure during adolescence would alter nucleus accumbens septi (NAcc) dopamine (DA) levels in the adult brain.

Methods: Rats were injected daily from postnatal day (PND) 30 to 50 with either 0.

Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi.

In humans, adolescent exposure to illicit drugs predicts the onset of adult drug abuse and suggests that early drug use potentiates vulnerability to drug addiction. Cocaine conditioned place preferences were measured in early adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them to environmental cues. Cocaine preferences were found for all ages at the high dose.

Nicotine administration significantly alters accumbal dopamine in the adult but not in the adolescent rat.

Many drug-dependent adults began using drugs during adolescence. In fact, adolescent drug users are more likely to become drug-dependent adults than those abstaining from drug use until after the age of 18. Because of this, recent research has begun to investigate the consequences of adolescent drug use.

Developmental differences in nicotine place conditioning.

To understand the motivations and implications of the prevalence of smoking, studies have compared the behavioral effects of nicotine, the psychoactive drug in tobacco, in adolescent and adult animals. The present study used a biased three-chambered conditioned-place preference procedure without prior habituation to examine the potential rewarding and anxiolytic effects of nicotine across adolescence and adulthood to assess the presence of age-dependent differences in response to nicotine.