Dosage and Conditioning Period Determine Reward or Aversion to Cannabis-induced Conditioned Place Preference in Sprague-Dawley Rats

Abstract

Objective: To assess the addictive potential of cannabis by investigating the motivational responses to low doses of delta-9-tetrahydrocannabinol (∆9-THC) and a marijuana tea extract (MTE), and to determine if the length of the conditioning period in the conditioned place preference (CPP) paradigm influences reward or aversion to these cannabinoid preparations. Methods: Thirty-eight Sprague-Dawley rats were taken through a biased CPP paradigm utilizing an eight-day schedule. The pre-conditioning phase consisted of three trials of 15 minutes each, and the conditioning phase lasted either 40 or 18 minutes in the drug-paired, ‘nonpreferred’ white chamber or the vehicle-paired, ‘preferred’ black chamber. Spontaneous motor activity (SMA) was used to determine the 18-minute conditioning period, dosage of a crude MTE and the oil-based vehicle for ∆9-THC (coconut oil), which did not alter the SMA of the rats. Differences in the mean times spent in the ‘non-preferred’ white chamber during the preconditioning and post-conditioning periods were compared using paired t-test. Results: Significant place aversion (p < 0.0001) to the MTE occurred at the 40-minute conditioning period, but not at the 18-minute period. Also, significant CPP reward (p < 0.01) to 0.05 mg/kg ∆9-THC occurred with the reduced 18-minute conditioning period, while a non-significant increase in post-conditioning time at the higher dose of 2.0 mg/kg ∆9-THC was obtained. Conclusion: Drug-seeking, motivational reward to 0.05 mg/kg ∆9-THC confirmed the addictive potential of ∆9-THC. However, the duration of the conditioning period in the CPP design was a determinant of the outcome to CPP-reward or -aversion to marijuana.