The effect of a unilateral g-hydroxydopamine (6-OHDA) lesion of the left medial forebrain bundle and 3 weeks treatment with L-DOPA of normal and 6-OHDA lesioned rats on CB1r mRNA expression was investigated by in situ hybridization. A 6-OHDA lesion of nigrostriatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA, did not alter CB1r mRNA levels in the dopamine depleted striatum. Similarly, chronic L-DOPA treatment of normal rats had no effect on striatal CB1r mRNA expression. In contrast, chronic L-DOPA treatment of 6-OHDA-lesioned rats significantly increased CB1r mRNA expression in the denervated striatum. These results suggest that the CB1r activity may be altered by L-DOPA's action and this may be related to the treatment of Parkinson's disease. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.