The effects of cannabidiol (CBD) on Δ9-tetrahydrocannabinol (THC) self-administration in male and female Long-Evans rats.

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

Adolescent delta-9-tetrahydrocannabinol (THC) exposure fails to affect THC-induced place and taste conditioning in adult male rats.

BACKGROUND: Adolescent initiation of drug use has been linked to problematic drug taking later in life and may represent an important variable that changes the balance of the rewarding and/or aversive effects of abused drugs which may contribute to abuse vulnerability. The current study examined the effects of adolescent THC exposure on THC-induced place preference (rewarding effects) and taste avoidance (aversive effects) conditioning in adulthood. METHODS: Forty-six male Sprague-Dawley adolescent rats received eight injections of an intermediate dose of THC (3.2mg/kg) or vehicle. After these injections, animals were allowed to mature and then trained in a combined CTA/CPP procedure in adulthood (PND ~90). Animals were given four trials of conditioning with intervening water-recovery days, a final CPP test and then a one-bottle taste avoidance test. RESULTS: THC induced dose-dependent taste avoidance but did not produce place conditioning. None of these effects was impacted by adolescent THC exposure. CONCLUSIONS: Adolescent exposure to THC had no effect on THC taste and place conditioning in adulthood. The failure to see an effect of adolescent exposure was addressed in the context of other research that has assessed exposure of drugs of abuse during adolescence on drug reactivity in adulthood.

Adolescent nicotine exposure fails to impact cocaine reward, aversion and self-administration in adult male rats.

The present experiments examined the effects of adolescent nicotine pre-exposure on the rewarding and aversive effects of cocaine and on cocaine self-administration in adult male rats. In Experiment 1, adolescent Sprague-Dawley rats (postnatal days 28-43) were given once daily injections of nicotine (0.6mg/kg) or vehicle and then tested for the aversive and rewarding effects of cocaine in a combined conditioned taste avoidance (CTA)/conditioned place preference (CPP) procedure in adulthood. In Experiment 2, adolescent Sprague-Dawley rats were pre-exposed to nicotine then tested for cocaine self-administration (0.25 or 0.75mg/kg), progressive ratio (PR) responding, extinction and cue-induced reinstatement in adulthood. In Experiment 1, rats showed significant dose-dependent cocaine-induced taste avoidance with cocaine-injected subjects consuming less saccharin over trials, but no effect of nicotine pre-exposure. For place preferences, cocaine induced significant place preferences with cocaine injected subjects spending significantly more time on the cocaine-paired side, but again there was no effect of nicotine history. All rats in Experiment 2 showed clear, dose-dependent responding during cocaine acquisition, PR testing, extinction and reinstatement with no effect of nicotine pre-exposure. These studies demonstrate that adolescent nicotine pre-exposure does not have an impact on cocaine's affective properties or its self-administration at least with the specific parametric conditions under which these effects were tested.

Measures of the aversive effects of drugs: A comparison of conditioned taste and place aversions.

The present experiments directly compared the ability of the conditioned taste and place aversion designs (CTA and CPA, respectively) to measure the aversive effects of lithium chloride (LiCl) in male Sprague-Dawley rats. In the CTA assessment (Experiment 1), rats were given one of two novel tastes paired with LiCl (0, 0.18, 0.32, 0.56 or 1mEq/kg) and the alternate novel taste paired with vehicle the next day. This was repeated three times, followed by a final two-bottle test. In the CPA assessment (Experiment 2), rats were given LiCl at the same doses and placed on one side of an unbiased two-chambered apparatus, followed by vehicle injection and placement on the opposite side on alternating days. This was repeated three times followed by free access to both sides in an assessment of relative preference. LiCl induced robust, dose-dependent taste aversions with rats receiving 0.32mEq/kg or greater consuming a smaller percentage of the drug-paired taste than that of controls. LiCl did not induce place aversions at any dose with LiCl- and vehicle-treated subjects displaying comparable preferences for the drug-paired side. The basis for the differences of the two designs in indexing LiCl's aversive effects was discussed.