40 research outputs found

    Sexual dimorphism in the neural impact of stress and alcohol

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    Alcohol use disorder is a widespread mental illness characterized by periods of abstinence followed by recidivism, and stress is the primary trigger of relapse. Despite the higher prevalence of alcohol use disorder in males, the relationship between stress and behavioral features of relapse, such as craving, is stronger in females. Given the greater susceptibility of females to stress-related psychiatric disorders, understanding sexual dimorphism in the relationship between stress and alcohol use is essential to identifying better treatments for both male and female alcoholics. This review addresses sex differences in the impact of stressors on alcohol drinking and seeking in rodents and humans. As these behavioral differences in alcohol use and relapse originate from sexual dimorphism in neuronal function, the impact of stressors and alcohol, and their interaction, on molecular adaptations and neural activity in males and females will also be discussed. Together the data reviewed herein, arising from a symposium entitled “Sex matters in stress-alcohol interactions” presented at the Fourth Volterra Conference on Stress and Alcohol, will highlight the importance of identifying sex differences to improve treatments for comorbid stress and alcohol use disorder in both populations

    Behavioral profiling of multiple pairs of rats selectively bred for high and low alcohol intake using the MCSF test

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    Genetic aspects of alcoholism have been modeled using rats selectively bred for extremes of alcohol preference and voluntary alcohol intake. These lines show similar alcohol drinking phenotypes but have different genetic and environmental backgrounds and may therefore display diverse behavioral traits as seen in human alcoholics. The multivariate concentric square field™ (MCSF) test is designed to provoke exploration and behaviors associated with risk assessment, risk taking and shelter seeking in a novel environment. The aim was to use the MCSF to characterize behavioral profiles in rat lines from selective breeding programs in the United States (P/NP, HAD1/LAD1, HAD2/LAD2), Italy (sP/sNP) and Finland (AA/ANA). The open field and elevated plus maze tests were used as reference tests. There were substantial differences within some of the pairs of selectively bred rat lines as well as between all alcohol-preferring rats. The most pronounced differences within the pairs of lines were between AA and ANA rats and between sP and sNP rats followed by intermediate differences between P and NP rats and minor differences comparing HAD and LAD rats. Among all preferring lines, P, HAD1 and HAD2 rats shared similar behavioral profiles, while AA and sP rats were quite different from each other and the others. No single trait appeared to form a common 'pathway' associated with a high alcohol drinking phenotype among all of the alcohol-preferring lines of rats. The marked behavioral differences found in the different alcohol-preferring lines may mimic the heterogeneity observed among human alcoholic subtypes

    A Genetic Animal Model of Alcoholism for Screening Medications to Treat Addiction

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    The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general

    Alterations in the seeking and self-administration of ethanol and anxiety-like behavior following exposure to yohimbine in rats selectively bred for high alcohol intake

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    Stress has been shown to contribute to alcohol drinking; however, inconsistencies in both the clinical and pre-clinical literature speak to the need for better paradigms to study this interaction. The present experiments compared animal models of the propensity to consume ethanol, the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) rat lines, in their response to yohimbine on ethanol seeking and self-administration and anxiety-like behavior. The P and HAD lines consume similar amounts of ethanol, yet differ in apparent motivation to drink ethanol, in anxiety-like behavior, and response to stress in alcohol drinking. Therefore, it was of interest to determine whether stress may differentially affect ethanol-motivated behaviors between the P and HAD lines. Acute administration of yohimbine, an &agr;-2 adrenoreceptor antagonist that increases anxiety and activate stress systems, increased operant ethanol self-administration and reinstatement of ethanol seeking in P rats, and free-choice ethanol drinking in both P and HAD rats. However, acute yohimbine administration decreased ethanol drinking when given limited access in the home cage, an effect that was diminished by extending the pre-treatment interval or increasing the number of ethanol exposure sessions. Yohimbine did not alter appetitive responding during a non-reinforced trial, nor did yohimbine alter the acquisition of free-choice ethanol drinking. Exposure to alcohol deprivation resulted in modest increases in ethanol intake, but yohimbine did not potentiate this effect. While acute yohimbine administration increased anxiety-like behavior, prior experience with repeated yohimbine exposures or with repeated deprivation periods did not. P rats were shown to be more active and less anxious and to display greater responding during a non-reinforced trial than HAD rats. Taken together, the results of these experiments demonstrate that the timing of yohimbine exposure relative to ethanol access is a critical component to determining its effects on ethanol seeking and self-administration and anxiety-like behavior. Further investigation into the parameters under which stress alters the motivation to seek and consume ethanol between these selectively bred lines is warranted, and future work that incorporates therapeutic agents aimed at reducing stress reactivity and alcohol drinking could elucidate effective strategies in the treatment of alcoholism
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