Dopaminergic Regulation of Cannabinoid Receptor mRNA Levels in the Rat Caudate-Plitamen: An In Situ Hybridization Study

Abstract: By quantitative in situ hybridization, we examined in vivo in the rat caudate-putamen the effects on levels of cannabinoid receptor mRNA of an interruption of dopamine neurotransmission for up to 1 month, by either 6-hydroxydopamine lesioning of the medial forebrain bundle or dopamine receptor blockade. We found, in a first set of experiments, that unilateral 6-hydroxydopamine dopa-minergic deafferentation of the striatum (characterized by a contralateral turning behavior in response to apomor-phine, the almost complete disappearance of the tyrosine hydroxylase hybridization signal in the substantia nigra, and an increase of preproenkephalin A mRNA level in the striatum) was associated with significantly increased (45%) cannabinoid receptor mRNA levels in the homolateral caudate-putamen. In a second set of experiments, treatments with the dopamine D₁ receptor antagonist SCH-23390, haloperidol, and the D₂ receptor antagonist sulpiride induced significantly higher cannabinoid receptor mRNA levels (respectively, 67, 34, and 27%) in the caudate-putamen. These observations suggest for the first time that, in vivo, cannabinoid receptor gene expression in the caudate-putamen is under the negative control of dopamine receptor-mediated events.