Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

Abstract

The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence.

Anxiolytic Effect of Voluntarily Consumed Alcohol in Sardinian Alcohol- Preferring Rats Exposed to the Social Interaction Test

“…Together, these results may be interpreted as P and sP rats "self-medicating" their inherent "anxiety" by voluntary alcohol drinking, modeling-to some extent-the relatively common clinical situation in which alcoholics are predisposed to alcohol drinking because of anxiety (the so-called "tension-reducing" hypothesis of etiology of excessive alcohol drinking) [18]. Because of their large variability in a number of alcohol-related traits and behaviors, selectively bred alcohol-preferring rat lines are often seen as possible experimental models of the different types, or typologies, of human alcoholics [1,3,8,19]. According to this hypothesis and taking into account the results of the EPM [4,17] and SI [present study] experiments, alcohol-preferring P and sP rats might represent proper models for those typologies of alcoholics in whom alcohol drinking is primarily driven by a search for anxiety relief [20,21].…”

“…After being temporarily deprived of alcohol, sP rats display relapse-like drinking [1] and loss of control over alcohol [2]. Notably, sP rats meet the fundamental criteria posed to define animal models of alcoholism [1,3].…”

Proteomic Approaches and Identification of Novel Therapeutic Targets for Alcoholism

“…Over the past decade, protein expression profiling has been used to identify alcoholresponsive proteins and associated pathways in different animal models of alcoholism. Rodents are the prime organisms of choice for modeling human diseases, and the genetically based propensity of some rats and mice to prefer and others to avoid alcohol has provided the basis for alcohol behavioral neuroscience preclinical research (Bell et al, 2012;Crabbe et al, 2010;Reilly et al, 2012).…”

Consumo De Álcool E a Influência Do Exercício Físico Na Atividade Enzimática De Ratos Wistar

“…Tem sido relatado em estudo com modelos animais que a atividade física de intensidade moderada aumenta as defesas antioxidantes das células 17 e promove o controle da hipertensão arterial 5 e das funções neurológicas 18 . De uma forma geral, induz uma melhora no funcionamento do organismo e das funções corporais prejudicadas, como o metabolismo hepático e as funções cognitivas 15,16 .…”