Cocaine-induced sex differences in D1 receptor activation and binding levels after acute cocaine administration

Eugene D. Festa, Shirzad Jenab, Jan Weiner, Arbi Nazarian, Tipyamol Niyomchai, Scott J. Russo, Lynne M. Kemen, Alaleh Akhavan, Hui Bing K. Wu, Vanya Quinones-Jenab

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Although it is established that female rats have a more robust behavioral response to acute cocaine administration than male rats, the neurobiological mechanisms underlying these differences remain unclear. The purpose of the present study was to determine whether dopamine (DA) receptor activation influences sex differences in cocaine-induced behaviors. A second study was performed to determine sex differences in D1/D2 receptor levels prior to and post-cocaine administration. Male and female Fischer rats were pre-treated with the D1 antagonist SCH-23390 (0.05, 0.1, and 0.25 mg/kg, i.p.), the D2 antagonist eticlopride (0.03, 0.1 mg/kg, i.p.), or vehicle (saline) 15 min before acute cocaine (20 mg/kg, i.p.) or saline administration. Cocaine-induced ambulatory and rearing activity was greater in female than male rats. Pre-treatment with SCH-23390 affected cocaine-induced ambulatory, rearing, and stereotypic activity in a sex-dependent manner; cocaine-induced ambulatory and stereotypic behavior in female rats was reduced by the lowest dose of SCH-23390. Eticlopride did not alter behavioral responses to cocaine in male or female rats. These results suggest that in both male and female rats, activation of the D1, but not the D2, receptor modulates cocaine's motor effects. There were no sex differences in baseline levels of D1, D2, and DA transporter binding in the caudate putamen (CPu) and the nucleus accumbens (NAc). Cocaine administration reduced D1 binding levels in the CPu only in male rats. Our findings suggest that the regulation of striatal D1 binding levels after acute cocaine administration is a sexually dimorphic process. We also hypothesize that the greater sensitivity to D1 receptor blockade in female rats, as compared to male rats, may contribute to their overall increased hyperactivity in response to acute cocaine. Taken together, the D1 receptor may be an important substrate in the regulation of sex differences to cocaine-induced locomotor activity.

Original languageEnglish
Pages (from-to)277-284
Number of pages8
JournalBrain Research Bulletin
Volume68
Issue number4
DOIs
StatePublished - 15 Jan 2006
Externally publishedYes

Keywords

  • Cocaine
  • Dopamine receptors
  • Female
  • Locomotor behavior
  • Sex differences

Fingerprint

Dive into the research topics of 'Cocaine-induced sex differences in D1 receptor activation and binding levels after acute cocaine administration'. Together they form a unique fingerprint.

Cite this