Highway to hell or magic smoke? The dose-dependence of ?9-THC in place conditioning paradigms.

ABSTRACT: The prerequisites for responsible cannabis use are at the heart of current inquiries into cannabis decriminalization by policy makers as well as academic and nonacademic stakeholders at a global scale. ?9-tetrahydrocannabinol (?9-THC), the prime psychoactive compound of the cannabis sativa, as well as cannabimimetics that resemble the pharmacological properties and psychological effects of ?9-THC, lend themselves handsomely to the preclinical scrutiny of reward-related behavior because they carry marked translational value. Although a functional dichotomy of the psychological effects of ?9-THC (rewarding versus aversive) has been abundantly reported in place conditioning (PC) paradigms, and might be best attributed to a dose-dependence of ?9-THC, most PC studies with ?9-THC feature no significant effects at all. Therefore, after decades of rigorous research, it still remains undetermined whether ?9-THC generally exerts rewarding or aversive effects in rodents. Here, we set out to extrapolate the commonly alleged dose-dependence of the rewarding and aversive effects of ?9-THC from the existing literature, at the behavioral pharmacological level of analysis. Specifically, our meta-analysis investigated: (i) the alleged bidirectional effects and dose-dependence of ?9-THC in the PC test; (ii) methodological inconsistencies between PC studies; and (iii) other pharmacological studies on cannabinoids (i.e., dopamine release, anxiety, stress, conditioned taste aversion, catalepsy) to substantiate the validity of PC findings. Our findings suggest that: (i) ?9-THC dose-dependently generates rewarding (1 mg/kg) and aversive (5 mg/kg) effects in PC; (ii) an inconsistent use of priming injections hampers a clear establishment of the rewarding effects of ?9-THC in PC tests and might explain the seemingly contradictory plethora of nonsignificant THC studies in the PC test; and (iii) other pharmacological studies on ?9-THC substantiate the dose-dependent biphasic effects of ?9-THC in PC. A standardized experimental design would advance evidence-based practice in future PC studies with ?9-THC and facilitate the pointed establishment of rewarding and aversive effects of the substance.

SUBMITTER: Kubilius RA 

PROVIDER: S-EPMC6097764 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature