Family history of alcoholism and response to amphetamine: sex differences in the effect of risk.
BACKGROUND
Individuals at risk for alcoholism exhibit an enhanced stimulant response to alcohol. It is not known whether individuals at risk also exhibit a heightened sensitivity to other drugs with stimulant properties.


METHODS
Healthy young men and women each received, in separate sessions, placebo and 10 mg of d-amphetamine in counterbalanced order. Stimulant and sedative subjective effects were recorded before and three times after capsule administration using the Biphasic Alcohol Effects Scale. The sample comprised 19 family-history-positive (FHP; 58% women) and 53 family-history-negative (FHN; 51% women) participants.


RESULTS
As compared with placebo, amphetamine increased ratings of stimulation in the sample as a whole. In addition, the ratings revealed an enhanced, as well as a protracted, stimulant response to amphetamine among FHP men, as compared with FHN men: for FHP men, ratings of stimulation made 3 and 6 hr after amphetamine administration were greater than baseline ratings. Moreover, in FHP men, the effect of amphetamine, as compared with placebo, was most evident 6 hr after capsule administration. In contrast, despite a dose x hour interaction in FHN men, post hoc comparisons revealed no differences between the baseline and any of the postamphetamine measurements or between amphetamine and placebo ratings at any of the time points. Among women, the drug effect did not differentiate the family-history groups.


CONCLUSIONS
Consistent with previous research on alcohol, high-risk men exhibited a heightened stimulant response to amphetamine. Thus, for men, sensitivity to the stimulant properties of drugs may be an endophenotype for alcoholism. Whereas the present results suggest that women at risk do not exhibit an enhanced stimulant response to amphetamine, further study is needed, including evaluation at various points in the menstrual cycle.
Gabbay
Frances H
FH
Clinical Psychophysiology and Psychopharmacology Laboratory, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA. fgabbay@usuhs.mil
D000328:Adult; D000437:Alcoholism / Q000235:genetics*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D012306:Risk; D012727:Sex Characteristics
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D000431:Ethanol; D003913:Dextroamphetamine