Voluntary alcohol drinking: Relation to corticosteroids and alcohol-mediated testosterone elevation

Alcohol dependence and alcoholism are modulated by environmental factors and genetic predisposition. Rat models have been invaluable in the investigation of several aspects of alcoholism in humans. The rodents exhibit a wide range of genetically determined alcohol-drinking preferences. Selective rat breeding programs with different alcohol preference has produced stable lines of rats that reliably exhibit high and low voluntary alcohol consumption (termed here AA and ANA, respectively). Alcohol consumption is also strongly dependent on environmental conditions. Stressful events evoke an extensive multisystem and integrative physiological response, where a major component is the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Testosterone has been implicated as mediator of the rewarding effect of alcohol, and the testosterone level is predictive of future alcohol consumption. The objective of the present thesis is to examine in greater detail the relations between alcohol, testosterone and neuroendocrine stress responses, and alcohol drinking. In the first study (I), the interrelations between endogenous and alcohol-mediated effects on testosterone and corticosterone levels and voluntary alcohol consumption were studied in a crossbred F2 generation of the original AA and ANA rat lines. The second study (II) was a reinvestigation of the effect of subchronic nandrolone decanoate treatment, which in an earlier study had been shown to increase alcohol consumption, and the relation of the effect on the HPA and hypothalamic-pituitarygonadal (HPG) axes. The third study (III) examined the possible role of benzyl alcohol, present as a preservative in the nandrolone product used in the earlier study, as a confounding factor that could explain differences between the results of the earlier study and the present one. In the fourth study (IV) the interrelations between the effect of corticosterone on alcohol-mediated testosterone changes and alcohol consumption in AA, ANA, F2 and Wistar rats were examined. The results of Study I shows connections between testosterone elevation and increased alcohol drinking, as well as between testosterone reduction and decreased alcohol drinking, which is in line with the original data of the AA and ANA lines. Elevated endogenous testosterone levels and higher frequencies of alcohol-induced testosterone increases were found in high consumption groups compared to low consumption groups. In Study II, subchronic nandrolone administration led to a reduction in alcohol-mediated testosterone levels, correlating with reduced voluntary alcohol consumption in the alcohol-preferring AA rat line. On the other hand, Study III showed that benzyl alcohol increases voluntary alcohol intake at least in the low-consumption rats, which may explain earlier discrepancies among studies. The results of Study IV were consistent with the hypothesis that corticosterone is involved in the regulation of alcohol-mediated testosterone changes. In conclusion, our present results suggests that corticosterone is a balancer, which regulates both the alcohol-mediated testosterone increase followed by reinforcement and increased voluntary alcohol drinking in high-drinking rats, and the alcohol-mediated testosterone reduction followed by disinforcement and reduced alcohol intake in low-drinking rats.