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Previous exposure to THC alters the reinforcing efficacy and anxiety-related effects of cocaine in rats.

Panlilio LV, Solinas M, Matthews SA, Goldberg SR

Department of Health and Human Services, Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.

The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol (THC) exposure, then allowing them to self-administer other drugs. In Experiment 1, THC pre-exposure did not alter the acquisition of cocaine self-administration or the amount of cocaine taken under a fixed-ratio 1 (FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine-seeking was significantly reduced in THC-exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive-ratio schedule, but it increased heroin self-administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC-exposed rats under FR1 heroin self-administration. When given cocaine, THC-exposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC pre-exposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effect-which was verified in Experiment 3 using another model of anxiety, the light-dark test-may explain the reduced reinforcing value of cocaine observed in THC-exposed rats in Experiment 1.

Published 15 February 2007 in Neuropsychopharmacology, 32(3): 646-57.
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