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Exposure to D-9-Tetrahydrocannabinol (THC) Increases Subsequent Heroin Taking but not Heroin’s Rei

Exposure to D-9-Tetrahydrocannabinol (THC) Increases Subsequent Heroin Taking but not Heroin’s Rei

  1. NeuroChi
    One concern about the widespread use of cannabis is that exposure to its active ingredient, D-9-tetrahydrocannabinol (THC), might
    increase future reinforcing effects of other abused drugs such as heroin. In this study, we investigated the effects of pre-exposure to THC
    on subsequent intravenous self-administration of heroin by Sprague–Dawley rats. In one group of rats, we studied (1) acquisition of
    heroin self-administration behavior using a continuous-reinforcement (fixed-ratio (FR) 1) schedule, (2) heroin dose–response
    relationships using an FR1/variable-dose schedule, and (3) reinforcing efficacy of heroin using a progressive-ratio schedule. The number of
    rats pre-exposed to THC that subsequently learned to self-administer 50 mg/kg injections of heroin within 10 daily sessions did not differ
    from vehicle-pretreated controls. In contrast, rats pre-exposed to THC subsequently self-administered significantly more heroin
    injections per session and showed significantly shorter post-injection pauses over a range of heroin doses (12.5–100 mg/kg/injection) using
    the variable-dose schedule. Interestingly, the maximum effort rats would exert to receive an injection of the different doses of heroin
    under the progressive-ratio schedule was not altered by THC pre-exposure. In a second group of rats, we varied the ‘price’ of heroin
    (responses required/dose), by manipulating FR response requirements at different doses of heroin across sessions, to calculate demand
    and response output curves. Again, consumption was significantly higher in the THC-treated rats at the lowest prices of heroin (FR1/
    100 mg/kg and FR1/50 mg/kg) but there were no differences in the reinforcing efficacy of heroin between THC- and vehicle-pretreated
    rats. Altogether, these results demonstrate that pre-exposure to THC alters some pharmacological effects of heroin that determine
    frequency of heroin taking, but offer no support for the hypothesis that pre-exposure to THC alters heroin’s efficacy as a reinforcer.