Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.

ABSTRACT

RATIONALE Fendiline is a GABAB receptor-positive allosteric modulator and L-type Ca²âº channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals OBJECTIVE: The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans METHODS: Following meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. RESULTS: Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p < 0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p < 0.05) or those that received two injections that corresponded to the last 2 days of the 10-day treatment (p < 0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. CONCLUSION: Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans.