Despite widespread cannabis use in humans, few rodent models exist demonstrating significant Δ⁹-tetrahydrocannabinol (THC) self-administration, possibly due to THC's co-occurring aversive effects, which impact drug reinforcement. Cannabis contains a number of phytocannabinoids in addition to THC, one of which, cannabidiol (CBD), has been reported to antagonize some of the aversive effects of THC. Given such effects of CBD, it is possible that it might influence THC intravenous self-administration in rodents. Accordingly, male and female Long-Evans rats were trained to self-administer THC over a 3-week period and then were assessed for the effects of CBD on responding for THC at 1:1 and 1:10 dose ratios or for the establishment of cocaine self-administration (as a positive control for drug self-administration). Consistent with previous research, THC self-administration was modest and only evident in a subset of animals (and unaffected by sex). Cocaine self-administration was high and evident in the majority of animals tested, indicating that the design was sensitive to drug reinforcement. There was no effect of CBD pretreatment on THC intravenous self-administration at any CBD:THC dose ratio. Future developments of animal models of THC self-administration and the examination of factors that affect its display remain important to establish procedures designed to assess the basis for and treatment of cannabis use and abuse. (PsycINFO Database Record
Background
α-pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP’s aversive and rewarding effects.
Methods
Male Sprague-Dawley rats were exposed to a novel saccharin solution, injected with one of four doses of α-PVP (0, 0.3, 1.0 and 3.0 mg/kg) (IP) and placed on one side of a place conditioning apparatus. The next day, they were injected with vehicle, given access to water and placed on the other side. Following four conditioning cycles, saccharin avoidance and place preferences were then assessed. The effects of α-PVP on body temperature were also examined.
Results
α-PVP induced dose-dependent taste avoidance as well as significant increases in time spent on the drug-paired side (although this effect was not dependent on dose). α-PVP also induced dose- and time-dependent hyperthermia.
Conclusions
α-PVP induced significant taste avoidance whose strength relative to the psychostimulants methylenedioxypyrovalerone (MDPV) and cocaine paralleled their relative binding to the dopamine transporter. Similar to other drugs of abuse, α-PVP has both aversive and rewarding effects. It will be important to assess how various experiential and subject variables impact these effects and their balance to predict abuse liability.
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