@article{ref1,
title="Highway to hell or magic smoke? The dose-dependence of Δ9-THC in place conditioning paradigms",
journal="Learning and memory",
year="2018",
author="Kubilius, Rimas A. and Kaplick, Paul M. and Wotjak, Carsten T.",
volume="25",
number="9",
pages="446-454",
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. Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC), the prime psychoactive compound of the <i>cannabis sativa</i>, as well as cannabimimetics that resemble the pharmacological properties and psychological effects of Δ<sup>9</sup>-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 Δ<sup>9</sup>-THC (rewarding versus aversive) has been abundantly reported in place conditioning (PC) paradigms, and might be best attributed to a dose-dependence of Δ<sup>9</sup>-THC, most PC studies with Δ<sup>9</sup>-THC feature no significant effects at all. Therefore, after decades of rigorous research, it still remains undetermined whether Δ<sup>9</sup>-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 Δ<sup>9</sup>-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 Δ<sup>9</sup>-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) Δ<sup>9</sup>-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 Δ<sup>9</sup>-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 Δ<sup>9</sup>-THC substantiate the dose-dependent biphasic effects of Δ<sup>9</sup>-THC in PC. A standardized experimental design would advance evidence-based practice in future PC studies with Δ<sup>9</sup>-THC and facilitate the pointed establishment of rewarding and aversive effects of the substance.<br><br>© 2018 Kubilius et al.; Published by Cold Spring Harbor Laboratory Press.<p /> <p>Language: en</p>",
language="en",
issn="1072-0502",
doi="10.1101/lm.046870.117",
url="http://dx.doi.org/10.1101/lm.046870.117"
}