TY - JOUR T1 - Motivational Effects of Cannabinoids Are Mediated by μ-Opioid and κ-Opioid Receptors JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1146 LP - 1154 DO - 10.1523/JNEUROSCI.22-03-01146.2002 VL - 22 IS - 3 AU - Sandy Ghozland AU - Hans W. D. Matthes AU - Frederic Simonin AU - Dominique Filliol AU - Brigitte L. Kieffer AU - Rafael Maldonado Y1 - 2002/02/01 UR - http://www.jneurosci.org/content/22/3/1146.abstract N2 - Repeated THC administration produces motivational and somatic adaptive changes leading to dependence in rodents. To investigate the molecular basis for cannabinoid dependence and its possible relationship with the endogenous opioid system, we explored Δ9-tetrahydrocannabinol (THC) activity in mice lacking μ-, δ- or κ-opioid receptor genes. Acute THC-induced hypothermia, antinociception, and hypolocomotion remained unaffected in these mice, whereas THC tolerance and withdrawal were minimally modified in mutant animals. In contrast, profound phenotypic changes are observed in several place conditioning protocols that reveal both THC rewarding and aversive properties. Absence of μ receptors abolishes THC place preference. Deletion of κ receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of μ- and κ-opioid receptors in modulating reward pathways forms the basis for the dual euphoric–dysphoric activity of THC. ER -