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PMID:16377433

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Citation

Festa, ED, Jenab, S, Weiner, J, Nazarian, A, Niyomchai, T, Russo, SJ, Kemen, LM, Akhavan, A, Wu, HB and Quinones-Jenab, V (2006) Cocaine-induced sex differences in D1 receptor activation and binding levels after acute cocaine administration. Brain Res. Bull. 68:277-84

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.

Links

PubMed Online version:10.1016/j.brainresbull.2005.08.023

Keywords

Animals; Cocaine/pharmacology; Female; Male; Models, Animal; Motor Activity/drug effects; Motor Activity/physiology; Rats; Rats, Inbred F344; Receptors, Dopamine D1/drug effects; Receptors, Dopamine D1/metabolism; Receptors, Dopamine D1/physiology; Salicylamides/pharmacology; Sex Characteristics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:DRD1

involved_in

GO:0048148: behavioral response to cocaine

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:DRD1

involved_in

GO:0007626: locomotory behavior

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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