Sex differences in striatal dopamine release in healthy adults.
BACKGROUND
Sex differences in addictive disorders have been described. Preclinical studies have implicated the striatal dopamine system in these differences, but human studies have yet to substantiate these findings.


METHODS
Using positron emission tomography (PET) scans with high-specific-activity [11C] raclopride and a reference tissue approach, we compared baseline striatal dopamine binding potential (BP) and dopamine release in men and women following amphetamine and placebo challenges. Subjective drug effects and plasma cortisol and growth hormone responses were also examined.


RESULTS
Although there was no sex difference in baseline BP, men had markedly greater dopamine release than women in the ventral striatum. Secondary analyses indicated that men also had greater dopamine release in three of four additional striatal regions. Paralleling the PET findings, men's ratings of the positive effects of amphetamine were greater than women's. We found no sex difference in neuroendocrine hormone responses.


CONCLUSIONS
We report for the first time a sex difference in dopamine release in humans. The robust dopamine release in men could account for increased vulnerability to stimulant use disorders and methamphetamine toxicity. Our findings indicate that future studies should control for sex and may have implications for the interpretation of sex differences in other illnesses involving the striatum.
Munro
Cynthia A
CA
Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
McCaul
Mary E
ME
Wong
Dean F
DF
Oswald
Lynn M
LM
Zhou
Yun
Y
Brasic
James
J
Kuwabara
Hiroto
H
Kumar
Anil
A
Alexander
Mohab
M
Ye
Weiguo
W
Wand
Gary S
GS
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000187:drug effects; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000187:drug effects; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects; D004292:Dominance, Cerebral / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000187:drug effects; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D012727:Sex Characteristics
D002250:Carbon Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D008694:Methamphetamine; D000661:Amphetamine; D004298:Dopamine