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We have shown that the 5-HT1A agonist R-(+)-hydroxy-2-(di- n-propylamino)tetralin [ R-(+)-8-OHDPAT] enhances motor activity in the monoamine-depleted rat, an acute model of Parkinson’s disease. The present work extends these findings by investigating motor effects of R-(+)-8-OHDPAT in the unilateral 6-hydroxydopamine-lesioned rat, a chronic model of Parkinson’s disease. The objectives of the present study were to assess the motor response to R-(+)-8-OHDPAT in rats with unilateral destruction of the nigrostriatal dopamine system and to determine the involvement of postsynaptic 5-HT1A receptors in this response. Rotational behavior after R-(+)-8-OHDPAT was investigated in rats that received 6-hydroxydopamine unilaterally into the median forebrain bundle 2 weeks before testing. A dose of 0.3 mg/kg subcutaneously (s.c.) R-(+)-8-OHDPAT induced significant ipsilateral turning in unilateral 6-OHDA-lesioned rats. Pretreatment with the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-2-pyridinyl-cyclohexanecarboxiamide maleate (WAY-100635, 0.1 mg/kg, s.c.) blocked turning. Blockade of 5-HT synthesis and 5-HT depletion caused by the tryptophan hydroxylase inhibitor dl- p-chlorophenylalanine did not decrease R-(+)-8-OHDPAT-induced turning. Finally, a subset of animals were tested for their turning response to the dopamine agonist apomorphine after tests with R-(+)-8-OHDPAT had been completed. Correlation analysis indicated no relationship existed between the turning response to apomorphine and the turning response to R-(+)-8-OHDPAT. R-(+)-8-OHDPAT induces ipsilateral turning in unilateral 6-OHDA lesioned rats by stimulating postsynaptic 5-HT1A receptors, not by altering 5-HT synthesis and release. The mechanism underlying the motor effects of R-(+)-8-OHDPAT appears to differ from classic dopaminergic anti-parkinsonian agents suggesting that 5-HT1A agonists might prove useful adjunctive therapy in the treatment of Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Examines the hypothesis that repeated daily administration of haloperidol leads to enhanced serotonin receptor signaling that is associated with increased vacuous chewing movements (VCM). Mechanisms that contribute to extrapyramidal side effects; Role of receptors in mediating dyskinetic activity associated with antipsychotic drug administration; Behavioral assessment of dyskinesias; Pharmacological analysis of VCM.

Presents a study to demonstrate that serotonin (5-hydroxytryptamine; 5-HT) 5-HT(1A) agonists can increase locomotor activity by activation of postsynaptic 5-HT(1A) heteroreceptors without the involvement of somatodendritic 5-HT(1A) autoreceptors, which are known to regulate 5-HT neuronal activity. Methods; Results; Conclusion that R-(+)-8-OHDPAT can increase motor activity in monoamine-depleted rats through postsynaptic 5-HT(1A) receptors.