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Motivational effects of cannabinoids are mediated by μ-opioid and k-opioid receptor
Ghozland, Sandy; Matthes, Hans W. D.; Simonin, Frederic; Filliol, Dominique; Kieffer, Brigitte L.; Maldonado, Rafael
Repeated THC administration produces motivational and somaticadaptive changes leading to dependence in rodents. Toinvestigate the molecular basis for cannabinoid dependenceand 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 THCinduced hypothermia, antinociception, and ypolocomotion 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.
02-07-2013
Cannabinoides -- Efectes fisiològics
Cannabinoides -- Receptors
Δ9-tetrahydrocannabinol
Place preference
Place aversion
Knock-out
Tolerance
Dependence
Reward
(c) 2002, Society for Neuroscience. The published version is available at: http://www.jneurosci.org/content/22/3/1146
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info:eu-repo/semantics/publishedVersion
Society for Neuroscience
         

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