The partial 5-HT(1A) agonist buspirone reduces the expression and development of l-DOPA-induced dyskinesia in rats and improves l-DOPA efficacy.
Dopamine (DA) replacement therapy with l-DOPA remains the standard pharmacotherapy for Parkinson's disease (PD). Unfortunately, chronic l-DOPA treatment is accompanied by development of motor fluctuations and l-DOPA-induced dyskinesia (LID). While serotonin (5-HT)(1A) agonists acutely reduce these complications, their prophylactic and long-term effects are not well-delineated. To test this, male Sprague-Dawley rats received unilateral 6-hydroxydopamine (6-OHDA) lesions. In experiment 1, l-DOPA-primed rats were pre-treated with Vehicle (0.9% NaCl), various doses of the partial 5-HT(1A) agonist, buspirone (0.25, 1.0 or 2.5 mg/kg, ip) or buspirone (2.5 mg/kg, ip)+the 5-HT(1A) antagonist, WAY100635 (0.5 mg/kg, ip) 5 min prior to l-DOPA (12 mg/kg+15 mg/kg benserazide, ip). Rats were tested for LID using the abnormal involuntary movements (AIMs) scale and motor performance using the forepaw adjusting steps test (FAS). In experiment 2, l-DOPA-naïve rats received co-administration of l-DOPA+buspirone (1.0 or 2.5 mg/kg, ip) for 2 weeks. AIMs and FAS were measured throughout. In l-DOPA-primed rats, buspirone dose-dependently reduced LID and improved l-DOPA-related motor performance due to action at the 5-HT(1A) receptor. In l-DOPA-naïve rats, buspirone delayed LID development while improving l-DOPA's anti-parkinsonian efficacy indicating the potential long-term benefits of 5-HT(1A) agonists for reduction of l-DOPA-related side effects.
Eskow
Karen L
KL
Behavioral Neuroscience Program, Department of Psychology, State University of New York at Binghamton, 4400 Vestal Parkway East, Binghamton, NY 13902-6000, USA.
Gupta
Vikas
V
Alam
Salmahn
S
Park
John Y
JY
Bishop
Christopher
C
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001545:Benserazide / Q000494:pharmacology; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002065:Buspirone / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003627:Data Interpretation, Statistical; D015259:Dopamine Agents / Q000627:therapeutic use* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000523:psychology; D007980:Levodopa / Q000627:therapeutic use* / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013565:Sympatholytics
D015306:Biogenic Monoamines; D015259:Dopamine Agents; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D002065:Buspirone