Genetic predisposition and exposure to alcohol and stress increase the risk for alcoholism, possibly by forming a threefold interaction. This is suggested by various aspects of alcohol-induced stress response dampening in offspring of alcoholics. We tested whether such an interaction is also revealed by prolactin secretion, which is predominantly controlled by hypothalamic dopamine. Plasma prolactin was measured during four experimental days in 26 young males with a paternal history of alcoholism (PHA) and in 22 family history negative (FHN) controls. A public speaking stress paradigm was applied on the first 2 days, and a non-stress acoustic startle experiment on the others. Before the tests, subjects drank alcohol (0.6 g/kg) or placebo in a randomized, double-blind crossover design. During placebo experiments, prolactin levels significantly increased after stress, but not after startle, and did not differ between risk groups. Alcohol administration significantly increased prolactin before stress and during startle in both groups, did not alter stress-induced prolactin stimulation in FHN, but significantly attenuated the prolactin stress response in PHA subjects. The alcohol effects on prolactin, cortisol, and adrenocorticotropin stress response were positively interrelated with each other. These data confirm that alcohol specifically dampens the stress response in PHA but not FHN subjects. Since prolactin responses to stress alone and alcohol alone were normal in PHA, we conclude that this genetic effect is not related to altered physiology of the hypothalamic dopaminergic system, but to risk-group specific alcohol effects on hierarchically higher brain areas controlling the stress response in general.

Genetic predisposition and exposure to alcohol and stress increase the risk for alcoholism, possibly by forming a threefold interaction. This is suggested by various aspects of alcohol-induced stress response dampening in offspring of alcoholics. We tested whether such an interaction is also revealed by prolactin secretion, which is predominantly controlled by hypothalamic dopamine. Plasma prolactin was measured during four experimental days in 26 young males with a paternal history of alcoholism (PHA) and in 22 family history negative (FHN) controls. A public speaking stress paradigm was applied on the first 2 days, and a non-stress acoustic startle experiment on the others. Before the tests, subjects drank alcohol (0.6 g/kg) or placebo in a randomized, double-blind crossover design. During placebo experiments, prolactin levels significantly increased after stress, but not after startle, and did not differ between risk groups. Alcohol administration significantly increased prolactin before stress and during startle in both groups, did not alter stress-induced prolactin stimulation in FHN, but significantly attenuated the prolactin stress response in PHA subjects. The alcohol effects on prolactin, cortisol, and adrenocorticotropin stress response were positively interrelated with each other. These data confirm that alcohol specifically dampens the stress response in PHA but not FHN subjects. Since prolactin responses to stress alone and alcohol alone were normal in PHA, we conclude that this genetic effect is not related to altered physiology of the hypothalamic dopaminergic system, but to risk-group specific alcohol effects on hierarchically higher brain areas controlling the stress response in general.