Serotonin 5-HT1-like receptors mediate hyperactivity in rats induced by 3,4-methylenedioxymethamphetamine.
This study was designed to evaluate the role of different serotonin (5-HT) receptor subtypes in mediating the effects of 3,4-methylenedioxymethamphetamine (MDMA) on rat exploration of a novel environment. The active enantiomer of MDMA, S-MDMA increases forward locomotion and suppresses investigatory behaviors and local movements. Previous studies indicate that S-MDMA-induced hyperactivity depends upon drug-induced 5-HT release. Propranolol and pindolol, beta-noradrenergic antagonists with affinity for 5-HT1 receptors, antagonized the S-MDMA-induced locomotor hyperactivity. The antagonism by propranolol was stereoselective. In contrast, a beta-noradrenergic antagonist that is a weaker antagonist of 5-HT receptors, betaxolol, was much less effective at blocking the behavioral response to S-MDMA. Among nonselective 5-HT antagonists, methiothepin was effective and methysergide and cyproheptadine were ineffective as antagonists of S-MDMA-induced hypermotility. In other systems, methiothepin has been found to be a good antagonist at 5-HT1B receptors where methysergide and cyproheptadine are ineffective. The 5-HT2 antagonist ritanserin was ineffective in blocking S-MDMA-induced hypermotility. However, ritanserin, methysergide, and cyproheptadine partially reversed the S-MDMA-induced suppression of investigatory responding, suggesting a contribution of 5-HT2 receptor activation to this component of the behavioral response to S-MDMA. This study indicates that S-MDMA produces a characteristic form of locomotor hyperactivity in rats that depends upon activation of 5-HT1-like receptors, possibly of the 5-HT1B subtype.
Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla 92093-0804.
C W
CW
Callaway
N
N
Rempel
R Y
RY
Peng
M A
MA
Geyer
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine