Serotonergic regulation of neuropeptide and glutamic acid decarboxylase mRNA levels in the rat striatum and globus pallidus: studies with fluoxetine and DOI

Abstract

The serotonergic regulation of neuropeptide and glutamic acid decarboxylase (GAD) mRNA levels in the rat basal ganglia was investigated by determining the effects of chronic treatment with the serotonin uptake blocker fluoxetine and the serotonin 5-HT 2 agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrobromide (DOI). Fluoxetine (10 mg/kg) induced a reduction of preproenkephalin and GAD65 mRNA levels in the caudate-putamen and nucleus accumbens core and shell after 5 days of treatment. In addition, GAD65 mRNA levels were reduced in the globus pallidus. These changes appeared to be transient as they were not found after 14 days of fluoxetine treatment. DOI (7 mg/kg), administered for 9 days, induced a decrease of preprodynorphin mRNA levels in the caudate-putamen and the nucleus accumbens core and shell. No regional differentiation in the effects of fluoxetine and DOI was observed. Based on the present results, we propose that an increased 5-HT tone may reduce enkephalin and GABA mRNA levels in striatal regions and in the globus pallidus. Our results further show that preproenkephalin mRNA is not affected by chronic 5-HT 2 receptor stimulation, indicating that the fluoxetine-induced decrease in preproenkephalin mRNA levels involves other 5-HT receptors than the 5-HT 2 receptor. Preprodynorphin mRNA levels, on the other hand, were found to be reduced after chronic 5-HT 2 receptor stimulation. This observation, together with our previous finding that the 5-HT 2 antagonist ritanserin tends to increase preprodynorphin mRNA levels, suggests a 5-HT 2-mediated tonic inhibition of preprodynorphin mRNA levels.