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

• Published in: Pharmacology, biochemistry and behavior Vol. 79; no. 3; pp. 391 - 400
• Main Authors: JACKSON, Michael J, AL-BARGHOUTHY, Ghassan, PEARCE, Ronald K. B, SMITH, Lance, HAGAN, James J, JENNER, Peter
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.11.2004
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - adverse effects; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; Behavioral psychophysiology; Biological and medical sciences; Callithrix; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced - prevention & control; Female; Fundamental and applied biological sciences. Psychology; Haloperidol - adverse effects; Haloperidol - pharmacology; Male; Motor Activity - drug effects; Motor Activity - physiology; Neurotransmission and behavior; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Receptor, Serotonin, 5-HT1B - physiology; Receptor, Serotonin, 5-HT1D - physiology; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Serotonin Antagonists - administration & dosage; Serotonin Receptor Agonists - administration & dosage; Animal model; Agonist; Neuroleptic; Psychotropic; Callithrix jacchus; Parkinson disease; Haloperidol; Involuntary movement; SB-224289-A; L-DOPA; Primates; Simioidea; Degenerative disease; Antagonist; Neurological disorder; Dyskinesia; Nervous system diseases; Dopamine antagonist; Butyrophenone derivatives; SKF-99101-H; Cerebral disorder; 5-HT1D serotonin receptor; Locomotion; Marmoset; Vertebrata; Animal activity; Mammalia; D2 Dopamine receptor; Animal; Central nervous system disease; 5-HT1B serotonin receptor; 5-HT1B receptors; Agonist antagonist; Extrapyramidal syndrome
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2004.07.015

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.