In rats, a genetic predisposition for excessive ethanol consumption is associated with alterations in central serotonergic activity. For example, ethanol-naïve P and HAD rats have significantly lower serotonin and/or 5HIAA5-hydroxyindoleacetic acid levels in the frontal cortex, nucleus accumbens, caudate putamen, hippocampus and hypothalamus compared with ethanol-naïve NP and LAD rats (Bell et al., 2012; Gongwer et al., 1989; Murphy et al., 1987). In addition, ethanol-naïve P, and in some cases ethanol-naïve HAD, rats have altered levels of 5HT1A, 5HT1B, 5HT2, 5HT2C and 5HT3 receptors in multiple brain regions compared with ethanol-naïve NP and LAD rats (McBride et al., 1997a; McBride et al., 1997b). Thus, alterations in receptor expression may be compensating for reduced serotonin function. Selective agonists and/or antagonists for various serotonin receptors affect the alcohol-consuming behavior of rats selected for high alcohol preference (Ding et al., 2012; Lankford et al., 1996; Lankford and Myers, 1996; Long et al., 1996; Overstreet et al., 1997; Rodd-Henricks et al., 2000; Rodd et al., 2010). Other selectively bred high alcohol-consuming rat lines (Alko Alcohol preferring and Sardinian alcohol preferring rats) had higher levels
