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Serotonin 2C (5‐HT2C) receptor inverse agonists elicit head bob behavior through a dopamine D1 receptor dependent mechanism
Author(s) -
Scarlota Laura,
Harvey John A,
Aloyo Vincent J
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.766.7
Subject(s) - ketanserin , inverse agonist , agonist , 5 ht2c receptor , endocrinology , medicine , receptor antagonist , dopamine , serotonin , receptor , pharmacology , dopamine receptor d1 , chemistry , 5 ht receptor , partial agonist , antagonist , endogenous agonist
Rabbit head bobs and rodent head twitches are behavioral assays of serotonin (5‐HT)2A receptor activation; each behavior can be elicited by DOI (a 5‐HT2A/2C agonist) and attenuated by ketanserin (a 5‐HT2A antagonist). 5‐HT2A receptor antagonists M100907 (M100) and MDL11939 (MDL) also elicit head bobs; however, these effects are distinguishable from DOI‐elicited responses as they are not blocked by ketanserin, suggesting a mechanism other than 5‐HT2A receptor activation. The current study examined the potential role of 5‐HT2C and dopamine (DA) receptors in inducing head bobs. Pre‐administration of the 5‐HT2C antagonist, SB242084 (1umol/kg, sc, 30 min) reduced head bobs elicited by both M100 (2.5umol/kg) and MDL (3umol/kg). Pretreatment of rabbits with the D1 antagonist SCH23390 (0.05umol/kg) also blocked M100 and MDL elicited head bobs. Moreover, administration of a D1 agonist, SKF38393 (9umol/kg) increased head bobs. To further characterize the role of 5‐HT2C receptors, we tested the response to a 5‐HT2C inverse agonist, SB206553. At a dose of 1umol/kg, we found no effect; however, a higher dose (3umol/kg) significantly increased head bobs. Consequently, head bobs may be considered an in vivo measure of 5‐HT2C inverse agonism. Finally, given the role of 5‐HT in DA release, we conclude that SB206553 , M100, and MDL all induce the same behavior through 5‐HT2C inverse agonist‐mediated activation of D1 receptors.