Attentional set shifting in HAP3, LAP3, and cHAP mice is unaffected by either genetic differences in alcohol preference or an alcohol drinking history

Abstract

Alcohol consumption may precede, or result from, behavioral inflexibility and contribute to individuals' difficulties ceasing drinking. Attentional set shifting tasks are an animal analog to a human behavioral flexibility task requiring recognition of a previous strategy as inappropriate, and the formation and maintenance of a novel strategy (Floresco, Block, & Tse, 2008). Abstinent individuals with alcohol use disorder, nonalcoholic individuals with a family history of alcoholism, and mice exposed to chronic-intermittent alcohol vapor show impaired behavioral flexibility (Gierski et al., 2013; Hu, Morris, Carrasco, & Kroener, 2015; Oscar-Berman et al., 2009). Behavioral flexibility deficits can be linked to frontal cortical regions connected to the striatum (Ragozzino, 2007), and alterations to the endocannabinoid system, implicated in drug seeking and consumption (Economidou et al., 2006; Serrano & Parsons, 2011), may affect these behaviors. Alcohol-preferring and nonpreferring rodents exhibit differences in CB1 receptor expression (CB1R; Hansson et al., 2007; Hungund & Basavarajappa, 2000), but whether dorsal striatal CB1Rs are important for other alcohol-related behaviors such as attentional set shifting tasks remains unclear. This study assesses whether selectively bred high (HAP) versus low alcohol-preferring mice differ in an operant attentional set shifting task or CB1R levels in the dorsal striatum and whether a history of voluntary alcohol consumption in crossed HAP mice exacerbates inflexibility. Contrary to our hypothesis, neither genetic differences in alcohol preference nor drinking affected set shifting. However, high alcohol-preferring mice-3 mice showed reduced levels of dorsal striatal CB1R compared with low alcohol-preferring-3 mice, suggesting that genetic differences in alcohol consumption may be mediated in part by striatal CB1R.