Modulation of striatal serotonin and opioid receptor mRNA expression following systemic N-methyl-norsalsolinol administration

The dihydroxylated tetrahydroisoquinoline derivative, 2(N)-methyl- norsalsolinol (NMNorsal), was identified in L-DOPA-treated patients with Parkinson's disease and proposed to be responsible for behavioral changes. In the present study, we investigated the effect of NMNorsal on serotonin and opioid receptors gene expression in caudate nucleus of Wistar rats. Using RT-PCR, serotonin 5-HT2A, μ- and δ-opioid receptor mRNA levels were determined after NMNorsal administration (40 mg/kg, i.p.). There was a marked increase of 5-HT2A and δ-opioid receptor mRNA levels with a maximum after 48 h. In contrast, μ-opioid receptor mRNA levels were significantly decreased to 10% after 24 h and 21% after 48 h, respectively. Our present results demonstrate for the first time that the atypical heterocylic L-DOPA/dopamine metabolite NMNorsal is able to modify long-term regulation of serotonin and opioid receptor expression in striatum. Since the occurrence of hallucinosis or psychosis following L-DOPA treatment is related to the serotonergic system, these results probably reflect a link between NMNorsal and L-DOPA side effects in Parkinson's disease. However, further experiments are needed.