Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice.
Serotonin(2C) (5-HT(2C)) receptors have been implicated to treat mood disorders such as depression and anxiety. In the present study, the capacities of two 5-HT(2C) agonists, MK212 and mCPP, to produce conditioned taste aversions in mice were evaluated. On two training days, Swiss-Webster male mice (19-34g) were trained to associate the flavor of a novel solution with the injection of various doses of MK212 or mCPP. On two alternate training days, mice were trained to associate a different flavored solution with an injection of saline. For testing, both flavored solutions were presented simultaneously and an avoidance of the MK212 or mCPP-paired solution indicated conditioned taste aversion. Robust conditioned taste aversions were observed to solutions paired with 1.0 or 10mg/kg MK212 or mCPP. Acquisition of conditioned taste aversions was blocked by nonselective serotonin antagonists cyproheptadine, bromo-LSD, metergoline, methysergide and mianserin. Selective 5-HT(2B/2C) antagonist SB206,553 blocked both MK212- and mCPP-induced conditioned taste aversion although selective 5-HT(2B/2C) antagonist SB200,646 only blocked mCPP-induced conditioned taste aversion. In a single-bottle procedure, MK212, bromo-LSD, and mianserin failed to alter acquisition rate of a LiCl-induced conditioned taste aversion. Taken together, these data indicate that the serotonin agonists MK212 and mCPP produce conditioned taste aversion and that these effects are mediated predominantly through 5-HT(2C) receptors.
Walker
Ellen A
EA
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 North Broad Street, Philadelphia, PA 19140, USA. ellen.walker@temple.edu
Kohut
Stephen J
SJ
Hass
Richard W
RW
Brown
Edward K
EK
Prabandham
Anupama
A
Lefever
Timothy
T
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D018021:Lithium Chloride / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D012054:Reinforcement, Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013649:Taste / Q000187:drug effects
D010879:Piperazines; D011719:Pyrazines; D044405:Receptor, Serotonin, 5-HT2C; D012702:Serotonin Antagonists; D008803:Mianserin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D008238:Lysergic Acid Diethylamide; D018021:Lithium Chloride; C084642:2-bromolysergic acid diethylamide; C015068:1-(3-chlorophenyl)piperazine