Effects of baclofen on maintenance and reinstatement of intravenous cocaine self-administration in rats.

Abstract

RATIONALE:

Recent studies suggest that the GABA(B) receptor agonist, baclofen, may be a useful pharmacotherapy for cocaine abuse.

OBJECTIVES:

To investigate further the effects of baclofen on maintenance and reinstatement of cocaine-reinforced behavior in rats.

METHODS:

Two groups of rats were trained to self-administer IV cocaine (0.2 or 0.4 mg/kg per infusion) during daily 7-h sessions under a fixed-ratio 1 schedule. Rats were pretreated with baclofen (1.25, 2.5 or 5 mg/kg IP) or saline before the session for 5 consecutive days. An additional group of rats was trained to self-administer IV cocaine (0.4 mg/kg per infusion) during the first 2 h of daily 7-h sessions. Cocaine was replaced by saline for the remaining 5 h of the session. Once behavior had stabilized over the 7-h period, priming injections of saline (IV), cocaine (3.2 mg/kg IV) or baclofen (1.25 or 2.5 mg/kg IP) were administered prior to hour 4. Injections of baclofen (1.25 or 2.5 mg/kg IP) or saline were also given before priming injections of cocaine.

RESULTS:

Pretreatment with the two higher doses of baclofen (2.5 and 5 mg/kg) decreased the number of cocaine infusions in both maintenance groups (0.2 and 0.4 mg/kg) over the 5-day treatment period. Baclofen had a greater suppressant effect on responding maintained by the lower dose of cocaine. Priming injections of baclofen (1.25 and 2.5 mg/kg) or saline did not reinstate responding. However, these same doses of baclofen dose-dependently reduced the reinstatement of responding produced by priming injections of cocaine.

CONCLUSIONS:

1) The magnitude of the suppressant effects of baclofen on maintenance of cocaine self-administration depends upon the maintenance dose, 2) baclofen may be useful in preventing reinstatement of cocaine-seeking behavior, and 3) compared to maintenance, reinstatement of responding is more sensitive to the suppressant effects of baclofen.

• Authors: U C Campbell, S T Lac, M E Carroll
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 143 Issue 2 Pg. 209-14 (Apr 1999) ISSN: 0033-3158 [Print] Germany
• PMID: 10326784 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dopamine Uptake Inhibitors
• GABA Agonists
• Baclofen
• Cocaine

Topics

• Animals
• Baclofen (pharmacology)
• Cocaine (administration & dosage, pharmacology)
• Dopamine Uptake Inhibitors (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• GABA Agonists (pharmacology)
• Injections, Intravenous
• Male
• Rats
• Rats, Wistar
• Self Administration