Serotonin 2A receptor antagonist treatment reduces dopamine D1 receptor-mediated rotational behavior but not L-DOPA-induced abnormal involuntary movements in the unilateral dopamine-depleted rat.
Previous experiments have demonstrated that serotonin (5-HT) 2A receptor antagonists suppress hyperkinetic behaviors associated with dopamine (DA) D1 receptor supersensitivity in rats with 6-hydroxydopamine (6-OHDA) lesions. Since l-DOPA induced dyskinesia (LID) may be mediated by over-sensitive D1-mediated signaling, the present study examined the effects of the selective 5-HT2A antagonist M100907 on LID behaviors in DA-depleted rats. Adult male Sprague-Dawley rats with unilateral 6-OHDA lesions received daily l-DOPA treatments to produce dyskinetic behaviors as measured by abnormal involuntary movements (AIMs) testing. In these animals, M100907 (0.01, 0.1 or 1.0mg/kg, ip) given 30 min before l-DOPA did not alter the appearance or intensity of AIMs behaviors. Because l-DOPA induced AIMs in rats are dependent upon D1 and D2 receptor activation, a second study was performed to determine if M100907 could suppress D1- or D2-mediated rotational behaviors. Contralateral rotations induced by the D1 agonist SKF82958 were significantly reduced by pre-treatment with M100907. However, M100907 was ineffective in reducing rotations induced by the D2 agonist quinpirole. The finding that M100907 suppresses rotations induced by D1, but not D2, agonists may provide a partial explanation for the lack of effect of a selective 5-HT2A antagonist on l-DOPA-induced AIMs behaviors.
Taylor
Jennifer L
JL
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Bishop
Christopher
C
Ullrich
Thomas
T
Rice
Kenner C
KC
Walker
Paul D
PD
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000172:deficiency; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020820:Dyskinesias / Q000188:drug therapy / Q000209:etiology; D005464:Fluorobenzenes / Q000008:administration & dosage*; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D045442:Rotarod Performance Test / Q000379:methods; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D013239:Stereotyped Behavior / Q000187:drug effects*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D005464:Fluorobenzenes; D010880:Piperidines; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; D007980:Levodopa; D016627:Oxidopamine; C079049:volinanserin; D004298:Dopamine