Sex differences in the effects of baclofen on the acquisition of intravenous cocaine self-administration in rats.
Baclofen, a GABA(B) agonist, decreases both the maintenance and reinstatement of i.v. cocaine-reinforced responding in rats. In the present experiment the effects of baclofen were extended to a comparison of male and female rats during the acquisition of i.v. cocaine self-administration. Four groups of rats were trained to self-administer i.v. cocaine (0.2 mg/kg) under a fixed-ratio 1 (FR 1) schedule using an autoshaping procedure. The criterion for acquisition was a 5-day period during which a mean of 100 cocaine infusions were administered. Rats were given 30 days to reach this criterion. Male and female groups (n=10-13) were pretreated with i.p. injections of baclofen (2.5 mg/kg) or vehicle 30-min prior to the sessions. A subset of rats (N=5) that did not acquire cocaine self-administration continued to be exposed to the acquisition procedure after baclofen treatment ended. Pretreatment with baclofen decreased both the rate of acquisition of cocaine self-administration and the percentage of rats meeting the acquisition criterion to a greater extent in females than in males. Female rats that did not meet the acquisition criterion with baclofen treatment, acquired within a few days after treatment ended. The findings confirm previous reports of enhanced acquisition of cocaine self-administration in females versus males, and they indicate that baclofen suppressed the acquisition of cocaine self-administration significantly more in females than in males.
Campbell
Una C
UC
Merck Research Laboratories, San Diego, 505 Coast Boulevard South, Suite 300, La Jolla, CA 92037, USA.
Morgan
Andrew D
AD
Carroll
Marilyn E
ME
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000523:psychology; D012727:Sex Characteristics
D018765:Dopamine Uptake Inhibitors; D018755:GABA Agonists; D001418:Baclofen; D003042:Cocaine