Effect of 5-HT1B/D receptor agonist and antagonist administration on motor function in haloperidol and MPTP-treated...

An interaction between brain serotonergic and dopaminergic systems involving 5-HT(1B) receptors may contribute to motor complications arising from the drug treatment of neurological and psychiatric disorders. This study assessed the effects of treatment with a non-selective 5-HT(1B/D) receptor agonist and a selective 5-HT(1B) receptor antagonist on akinesia induced in marmosets by long-term treatment with haloperidol and on motor disability and l-3, 4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. In marmosets treated chronically with haloperidol, the 5-HT(1B) agonist SKF-99101-H reduced locomotor activity and induced motor disability, whereas the 5-HT(1B) antagonist SB-224289-A had no effect on motor behaviour. Haloperidol administration induced a suppression of locomotor activity which was not reversed by co-administration of either SKF-99101-H or SB-224289-A. In MPTP-treated common marmosets, neither SKF-99101-H nor SB-224289-A induced any significant change in motor function. However, SKF-99101-H inhibited L-DOPA-induced dyskinesia and the reversal of motor deficits whereas SB-224289-A was without effect. The results of this study indicate that the 5-HT(1B) receptor appears not to be an appropriate target for the treatment of Parkinson's disease (PD) or for the control of drug-induced motor complications developed as a tong-term consequence of neuroleptic or L-DOPA treatment.