Sex differences in cocaine-induced behavioral responses, pharmacokinetics, and monoamine levels.
Female rats display a more robust behavioral response to acute cocaine administration than do male rats. However, a clear understanding of the biological mechanisms underlying these differences remains elusive. The present study investigated whether sexual dimorphisms in cocaine-induced motor behavior might be based on monoaminergic levels and/or cocaine pharmacokinetics. An acute injection of cocaine (5, 15, 20 or 30 mg/kg) or saline was administered to male and female rats, and behavioral activity was monitored for 3 h. Following acute cocaine or saline administration motor behavior varied according to dose and sex; overall, female rats displayed greater rearing counts and stereotypic scores, greater total locomotor counts at 15, 20, and 30 mg/kg of cocaine, and greater ambulatory counts at 20 and 30 mg/kg of cocaine than did male rats. Neurochemical determinations in post-mortem tissue showed that both male and female rats had increases in total dopamine (DA) in the caudate putamen (CPu) 15 min following cocaine administration. Additionally, male rats had a decrease in dihydroxyphenylacetic acid (DOPAC)/DA turnover. Female rats showed significant reductions in total levels of DA, DOPAC, HVA, serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and DOPAC/DA turnover in the nucleus accumbens (NAc). Male rats displayed a reduction only in DOPAC/DA turnover and increases in 5-HT in the NAc following cocaine administration. Furthermore, sex differences in cocaine metabolism were observed where females had greater brain/blood levels of norcocaine and ecgonine methyl ester while male rats had higher blood levels of benzoylecgonine. These results suggest that sex differences in the behavioral responses to cocaine administration could be explained in part by intrinsic differences in both monoaminergic levels and metabolic processes.
Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA.
Eugene D
ED
Festa
Scott J
SJ
Russo
Farhad M
FM
Gazi
Tipyamol
T
Niyomchai
Lynne M
LM
Kemen
Shen-Nan
SN
Lin
Rodger
R
Foltz
Shirzad
S
Jenab
Vanya
V
Quinones-Jenab
D000818:Animals; D015306:Biogenic Monoamines / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
D015306:Biogenic Monoamines; D003042:Cocaine