Individual differences in voluntary ethanol consumption lead to differential activation of the central amygdala in rats: relationship to the anxiolytic and stimulant effects of low dose ethanol.

Abstract

Although alcohol use disorders and anxiety disorders are highly comorbid, the relationship between these 2 disorders is not fully understood. Previous work from our laboratory shows that anxiety-like behavior is highly variable in outbred Long-Evans rats and is related to the level of voluntary ethanol (EtOH) consumption, suggesting that basal anxiety state influences EtOH intake. To further examine the relationship between the acquisition of EtOH consumption and anxiety phenotype, Long-Evans rats were assessed for anxiety-like behavior and neuronal activation following voluntary EtOH consumption in a limited access drinking paradigm. Rats were allowed to self-administer EtOH (6% v/v) for 4 days using a limited access drinking in the dark paradigm and divided into high- and low-drinking groups based on a median split of average daily EtOH intake. Immediately following the fourth drinking session, animals were tested on the elevated plus maze and evaluated for anxiety-like behaviors. Fos immunoreactivity was assessed in the central and basolateral amygdala, as well as the bed nucleus of the stria terminalis. High EtOH drinkers spent significantly more time on the open arms of the plus maze than low EtOH drinkers. High EtOH drinkers also had increased locomotor activity as compared to both low EtOH drinkers and water drinkers. Fos immunoreactivity was positively correlated with EtOH consumption in all brain regions examined, although Fos-positive cell counts were only significantly different between high and low EtOH drinkers in the central amygdala (CeA). Our findings demonstrate that outbred rats will voluntarily consume behaviorally effective doses of EtOH in a short-term access model and EtOH consumption is positively correlated with increased neuronal activation in the CeA.