The alcohol-preferring (P) and high-alcohol-drinking (HAD) rats – Animal models of alcoholism

Abstract

The objective of this article is to review the literature on the utility of using the selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats in studies examining high alcohol drinking in adults and adolescents, craving-like behavior, and the co-abuse of alcohol with other drugs. The P line of rats meets all of the originally proposed criteria for a suitable animal model of alcoholism. In addition, the P rat exhibits high alcohol-seeking behavior, demonstrates an alcohol deprivation effect (ADE) under relapse drinking conditions, consumes amounts of ethanol during adolescence equivalent to those consumed in adulthood, and co-abuses ethanol and nicotine. The P line also exhibits excessive binge-like alcohol drinking, attaining blood alcohol concentrations (BACs) of 200 mg% on a daily basis. The HAD replicate lines of rats have not been as extensively studied as the P rats. The HAD1,2 rats satisfy several of the criteria for an animal model of alcoholism, e.g., these rats will voluntarily consume ethanol in a free-choice situation to produce BACs between 50–200 mg%. The HAD1,2 rats also exhibit an ADE under repeated relapse conditions, and will demonstrate similar levels of ethanol intake during adolescence as seen in adults. Overall, the P and HAD1,2 rats have characteristics attributed to an early onset alcoholic, and can be used to study various aspects of alcohol use disorders.

Alcohol, stress hormones, and the prefrontal cortex: A proposed pathway to the dark side of addiction

“…Non-dependent alcohol use can escalate to a pattern of abuse that may be brought on by additional factors such as social pressure, age, genetic predispositions, and gender (Chassin et al, 2004; Oei and Morawska, 2004; Ceylan-Isik et al, 2010; Silveri, 2012). Many of these same factors influence drinking patterns in rodents, and these preclinical models have aided in the identification of some of the neural correlates of risky drinking (Anacker and Ryabinin, 2010; Sherrill et al, 2011; Gilpin et al, 2012; Karanikas et al, 2013; McBride et al, 2014). …”

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking

“…The rederived P, NP, and HAD rats used here have been bred over many generations as a rodent model to investigate the genetic basis of excessive alcohol consumption by humans (Czachowski and Samson, 2002;McBride et al, 2014). These lines have been both behaviorally and neurobiologically characterized and show phenotypic differences in their responses to ethanol that may be of relevance to the neurogenetic mechanisms underlying ethanol preference or nonpreference (McBride et al, 2014).…”

“…These lines have been both behaviorally and neurobiologically characterized and show phenotypic differences in their responses to ethanol that may be of relevance to the neurogenetic mechanisms underlying ethanol preference or nonpreference (McBride et al, 2014). For example, P rats have a lesser aversive response to ethanol in a conditioned taste aversion procedure (Froehlich et al, 1988) and may show more anxiety-like behavior in an EPM compared with NP rats (Stewart et al, 1993), the latter observation being confirmed in the rP cohorts studied here, although this high-anxiety phenotype is not always observed (Viglinskaya et al, 1995).…”

“…Thus, alcohol-preferring (P) and high-alcohol-drinking (HAD) lines have been established on the basis of their preference for a 10% alcohol solution over water and their consumption of 45 g of alcohol/kg body weight/day. Both P and HAD lines have been shown to drink ethanol under free-choice conditions (McBride et al, 2014), to be highly motivated for ethanol compared with alcohol-nonpreferring (NP) rats, and to readily acquire instrumental responding for ethanol (Czachowski and Samson, 2002).…”

Reduction of alcohol drinking of alcohol-preferring (P) and high-alcohol drinking (HAD1) rats by targeting phosphodiesterase-4 (PDE4)

“…Disparities in the effects of PDE4 inhibitors to alter EtOH drinking in the two rat lines could be associated with their distinct genetic backgrounds (cf. Bell et al 2012; McBride et al 2014). Thus, the innately higher expression levels of Pde4a and Pde4b in the NAc shell of P vs NP, but not HAD1 vs LAD1, rats observed in Exp 4 of the present study (Table 4) may indicate that the PDE4 system is more involved in EtOH intake by P vs HAD1 rats.…”