Dissociation of genetic and hormonal influences on sex differences in alcoholism-related behaviors.
Differences between men and women in alcohol abuse prevalence have long been attributed to social and hormonal factors. It is, however, becoming apparent that sex differences in substance dependence are also influenced by genetic factors. Using a four core genotype mouse model that enables dissociation of chromosomal and gonadal sex, we show that habitual responding for alcohol reinforcement is mediated by sex chromosome complement independent of gonadal phenotype. After moderate instrumental training, chromosomal male (XY) mice became insensitive to outcome devaluation, indicating habitual responding. Chromosomal female (XX) mice remained sensitive to outcome devaluation, signifying goal-directed behavior. There was no effect of gonadal phenotype on habitual responding. Conversely, alcohol drinking was predicted by gonadal phenotype independent of sex chromosome complement. These results indicate that different alcoholism-related behaviors are determined independently by gonadal and chromosomal sex.
Barker
Jacqueline M
JM
Department of Psychiatry, Yale University, Connecticut Mental Health Center, New Haven, Connecticut 06519, USA.
Torregrossa
Mary M
MM
Arnold
Arthur P
AP
Taylor
Jane R
JR
D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D005260:Female; D005518:Food Preferences / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009919:Orchiectomy / Q000379:methods; D012055:Reinforcement Schedule; D012727:Sex Characteristics; D012729:Sex Chromosome Aberrations; D012730:Sex Chromosomes; D051876:Sex-Determining Region Y Protein / Q000235:genetics
D002492:Central Nervous System Depressants; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D000431:Ethanol