Individual Differences in Ethanol Self‐Administration Following Withdrawal Are Associated With Asymmetric Changes in Dopamine and Serotonin in the Medial Prefrontal Cortex and Amygdala

Abstract

Ethanol withdrawal alters brain neurochemistry, causes asymmetric activation of neurons in the medial prefrontal cortex (mPFC) and amygdala (AMY), and increases ethanol craving and drinking. Rats with intrinsic rightward-turning preferences drink more ethanol than those with left or no preferences; they also exhibit an ethanol-induced neurochemical activation that favors the right side of the mPFC. Our experiments used rats with different turning preferences to assess differences in withdrawal effects on mPFC and AMY neurochemistry as well as ethanol self-administration. Rats with left-turning, right-turning, and nonturning preferences were fed a 6% ethanol-containing liquid diet (WD) or a pair-fed control diet for 14 days. Differences in dopamine (DA), serotonin (5HT), norepinephrine (NE), and metabolite [3,4-dihydroxphenylacetic acid, homovanillic acid (HVA), and 5-hydroxyindoleacetic acid) concentrations were assessed in each side of the mPFC and AMY during acute withdrawal. Similar groups were fed the same diets and tested for consumption of 10% ethanol versus water and 1% sucrose versus water. WD increased HVA/DA in the mPFC and caused depletions of DA and 5HT in the mPFC and 5HT in the AMY. These effects were greater in the right than in the left side of these structures in rats with right-turning preferences. WD reduced ethanol drinking but right turners drank significantly more than left turners on day 2 of testing and drank more on days 2 and 3 than on day 1. No effects were observed on sucrose drinking. Similar groups were also trained to self-administer ethanol using a sucrose-fade sipper tube procedure that separated measures of ethanol seeking (bar pressing) and consumption. Following 14 days of vapor chamber exposure to ethanol, rats of all turning preferences had a lower rate of bar pressing on the first postwithdrawal day and shorter latencies to begin bar pressing on the third withdrawal day versus prewithdrawal baseline. Only right-turning-preference rats consumed more ethanol following withdrawal. These studies show that individual rats differ in postwithdrawal brain neurochemistry and ethanol consumption and that these differences are associated with differences in functional brain asymmetry.