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 behavi...
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Published in | Neuropharmacology Vol. 46; no. 5; pp. 672 - 687 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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England
Elsevier Ltd
01.04.2004
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Abstract | 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. |
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AbstractList | 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. |
Author | Niyomchai, Tipyamol Quinones-Jenab, Vanya Festa, Eugene D. Russo, Scott J. Foltz, Rodger Gazi, Farhad M. Lin, Shen-Nan Jenab, Shirzad Kemen, Lynne M. |
Author_xml | – sequence: 1 givenname: Eugene D. surname: Festa fullname: Festa, Eugene D. organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 2 givenname: Scott J. surname: Russo fullname: Russo, Scott J. organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 3 givenname: Farhad M. surname: Gazi fullname: Gazi, Farhad M. organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 4 givenname: Tipyamol surname: Niyomchai fullname: Niyomchai, Tipyamol organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 5 givenname: Lynne M. surname: Kemen fullname: Kemen, Lynne M. organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 6 givenname: Shen-Nan surname: Lin fullname: Lin, Shen-Nan organization: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA – sequence: 7 givenname: Rodger surname: Foltz fullname: Foltz, Rodger organization: Center for Human Toxicology, Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA – sequence: 8 givenname: Shirzad surname: Jenab fullname: Jenab, Shirzad organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA – sequence: 9 givenname: Vanya surname: Quinones-Jenab fullname: Quinones-Jenab, Vanya email: jenab@genectr.hunter.cuny.edu organization: Department of Psychology, Hunter College, The City University of New York, 695 Park Avenue, New York, NY 10021, USA |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/14996545$$D View this record in MEDLINE/PubMed |
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Keywords | Cocaine Dopamine Gender Serotonin Metabolism Sex |
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58 Jenab (10.1016/j.neuropharm.2003.11.017_BIB25) 2002; 58 Pettit (10.1016/j.neuropharm.2003.11.017_BIB39) 1990; 55 Van Haaren (10.1016/j.neuropharm.2003.11.017_BIB51) 1991; 39 Renner (10.1016/j.neuropharm.2003.11.017_BIB41) 1984; 34 Russo (10.1016/j.neuropharm.2003.11.017_BIB44) 2003; 120 Tropp (10.1016/j.neuropharm.2003.11.017_BIB50) 2001; 119 Liu (10.1016/j.neuropharm.2003.11.017_BIB31) 2003; 90 Perrotti (10.1016/j.neuropharm.2003.11.017_BIB38) 2000; 291 Hyman (10.1016/j.neuropharm.2003.11.017_BIB24) 2001; 2 Walker (10.1016/j.neuropharm.2003.11.017_BIB55) 2002; 73 Bowman (10.1016/j.neuropharm.2003.11.017_BIB7) 1999; 290 Zhang (10.1016/j.neuropharm.2003.11.017_BIB57) 1996; 59 Carlsson (10.1016/j.neuropharm.2003.11.017_BIB13) 1987; 12 Galloway (10.1016/j.neuropharm.2003.11.017_BIB22) 1990; 6 Bisagno (10.1016/j.neuropharm.2003.11.017_BIB59) 2002; 940 Einhorn (10.1016/j.neuropharm.2003.11.017_BIB19) 1988; 8 Walker (10.1016/j.neuropharm.2003.11.017_BIB54) 2001; 297 Chang (10.1016/j.neuropharm.2003.11.017_BIB14) 1999; 861 Broderick (10.1016/j.neuropharm.2003.11.017_BIB9) 1997; 21 Chen (10.1016/j.neuropharm.2003.11.017_BIB15) 2002; 68 Etgen (10.1016/j.neuropharm.2003.11.017_BIB20) 2002 Walker (10.1016/j.neuropharm.2003.11.017_BIB53) 2001; 25 Baumann (10.1016/j.neuropharm.2003.11.017_BIB2) 1998; 44 Boyd (10.1016/j.neuropharm.2003.11.017_BIB8) 1993; 10 Ritz (10.1016/j.neuropharm.2003.11.017_BIB42) 1987; 4819 Mendelson (10.1016/j.neuropharm.2003.11.017_BIB32) 1999; 21 Bisagno (10.1016/j.neuropharm.2003.11.017_BIB5) 2003; 74 Morishima (10.1016/j.neuropharm.2003.11.017_BIB35) 1993; 122 Lin (10.1016/j.neuropharm.2003.11.017_BIB29) 2001; 25 Chin (10.1016/j.neuropharm.2003.11.017_BIB17) 2002; 945 Becker (10.1016/j.neuropharm.2003.11.017_BIB4) 1981; 204 Parsons (10.1016/j.neuropharm.2003.11.017_BIB36) 1993; 606 Russo (10.1016/j.neuropharm.2003.11.017_BIB43) 2003; 970 |
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SubjectTerms | Animals Biogenic Monoamines - blood Biogenic Monoamines - metabolism Brain - drug effects Brain - metabolism Cocaine Cocaine - blood Cocaine - pharmacokinetics Cocaine - pharmacology Dopamine Dose-Response Relationship, Drug Female Gender Male Metabolism Motor Activity - drug effects Motor Activity - physiology Rats Rats, Inbred F344 Serotonin Sex Sex Characteristics |
Title | Sex differences in cocaine-induced behavioral responses, pharmacokinetics, and monoamine levels |
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