Exposure to Δ-9-Tetrahydrocannabinol (THC) Increases Subsequent Heroin Taking but not Heroin's Reinforcing Efficacy: A Self-Administration Study in Rats

Abstract

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.

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

“…Under this schedule, the response requirement increases exponentially with each successive injection. The behavior of THC-exposed and vehicle-exposed rats did not differ under the progressive-ratio schedule, indicating that THC pre-exposure did not alter the reinforcing efficacy of heroin (Solinas et al, 2004). Thus, these results suggest that individuals with a history of THC exposure might take heroin more frequently if it were freely available, but they would not work harder than non-exposed individuals to obtain heroin if the cost were increased.…”

“…To this end, we recently evaluated the effects of tetrahydrocannabinol (THC) exposure on subsequent selfadministration of heroin in rats (Solinas et al, 2004). Using a regimen of THC pre-exposure that had earlier been shown to enhance the locomotor-activating effects of THC or morphine (Cadoni et al, 2001), rats were injected six times with THC or vehicle over 3 days.…”

“…Thus, to determine whether a history of THC preexposure alters the reinforcing effects of cocaine, we applied the same general procedure used earlier to study heroin self-administration (Solinas et al, 2004). Thus, in Experiment 1, rats were exposed to THC or vehicle for 3 days, ending 1 week before they were trained to self-administer cocaine under an FR1 schedule.…”

Adolescent Cannabis Exposure Alters Opiate Intake and Opioid Limbic Neuronal Populations in Adult Rats

“…Although the vehicle-exposed rats showed a higher percent increase in active responses than the THC rats, the behavior was not discriminative to the active lever since the control rats also had a higher increase in responding on the inactive lever. Using a progressive ratio self-administration paradigm, Solinas et al (2004a) showed that adult exposure to THC does not alter the incentive value of heroin even though the rats increased heroin intake. There may of course be differences in the incentive value of heroin in association with adolescent as compared to adult THC exposure, so altered motivation to self-administer the drug in a progressive ratio paradigm cannot be completely excluded.…”

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

“…As with the consumption of nondrug reinforcers, the consumption of drugs (eg ethanol, phencyclidine, cocaine, heroin) decreases in the face of increasing prices in both rats (eg Comer et al, 1996;Solinas et al, 2004;Heyman et al, 1999) and monkeys (Carroll et al, 1991;Carroll, 1996, 1997;Ko et al, 2002) (for a general review, Bickel et al, 1995). In the majority of studies, the demand for drug is initially inelastic to changes in price and then becomes elastic above a certain price, called P max (Hursh, 1991;Bickel et al, 2000).…”