Differential effects of 5-HT2C receptor ligands on place conditioning and locomotor activity in rats.
Effects of the 5-hydroxytryptamine (5-HT)(1A/1B/2C) receptor agonist N-[3-(trifluoromethyl)phenyl] piperazine (TFMPP, 0-3.0 mg/kg s.c.) and the 5-HT2C receptor agonist 8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY 161503, 0-3.0 mg/kg s.c.) in place conditioning were measured in male Sprague-Dawley rats. Effects of TFMPP, alone and with the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinyl-cyclohexanecarboxamine (WAY 100635), the 5-HT(1B) receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1'-biphenyl-4-carboxamide (GR 127935) or the 5-HT2C receptor antagonist 6-chloro-5-methyl-1-[[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl]indoline (SB 242084) and of WAY 161503 alone and with SB 242084 on locomotor activity were also assessed. Neither TFMPP nor WAY 161503 induced place conditioning. WAY 161503 (1.0 and 3.0 mg/kg s.c.) decreased locomotor activity; SB 242084 (1.0 mg/kg i.p.) blocked this effect. Reduced locomotor activity following TFMPP was blocked by SB 242084 but not WAY 100635 (0.1 mg/kg s.c.) or GR 127935 (3.0 mg/kg s.c.). Behaviourally relevant levels of 5-HT2C receptor stimulation may not exert reinforcing effects, although other studies indicate that such manipulations alter reinforcing effects of drugs of abuse.
Mosher
Tera
T
W.G. Dewhurst Laboratory, Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, 1E7.44 WMC, University of Alberta, Edmonton, AB, Canada T6G 2R7.
Hayes
David
D
Greenshaw
Andrew
A
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C502777:8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one; D000631:Aminopyridines; D007211:Indoles; D008024:Ligands; D010069:Oxadiazoles; D010879:Piperazines; D011719:Pyrazines; D011725:Pyridines; D011810:Quinoxalines; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C018406:1-(3-trifluoromethylphenyl)piperazine; C090701:GR 127935; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide