5-HT-dependent myoclonus in guinea pigs: mediation through 5-HT1A-5-HT2 receptor interaction.
Investigations utilizing agonists for 5-HT receptor subtypes have been conducted to determine which 5-HT receptor subtype(s) subserve myoclonus in the guinea pig. Administration of a nonselective 5-HT agonist such as 5-MeODMT (5-HT1A/5-HT2 agonist) induces a dose-dependent behavior characterized by head jerking at low doses (1-2 mg/kg, SC) and full-blown myoclonus (continuous rhythmic whole-body jerking) at higher doses (2.5-5 mg/kg, SC). In contrast, the selective 5-HT1A receptor agonist 8-OH-DPAT and the selective 5-HT2 receptor agonist DOI do not induce myoclonus, and elicit only limited head jerking across an otherwise behaviorally active range of doses (1-5 mg/kg, SC). Importantly, the coadministration of both 8-OH-DPAT and DOI results in the emergence of dose-dependent myoclonic behavior. These data suggest that coactivation of 5-HT1A and 5-HT2 receptors may be required for the induction of myoclonus in the guinea pig.
Eison
A S
AS
CNS Drug Discovery, Bristol-Myers Squibb Company, Wallingford, CT 06492.
Wright
R N
RN
Freeman
R P
RP
Gylys
J A
JA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009207:Myoclonus / Q000503:physiopathology* / Q000523:psychology; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000662:Amphetamines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D016713:Ritanserin; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine