Aversive stimulus properties of the 5-HT2C receptor agonist WAY 161503 in rats.
Serotonin2C (5-HT2C) receptors may influence motivation and reward through effects on the mesocorticolimbic dopamine (DA) system. Previous work from this laboratory indicated that 5-HT2C receptor stimulation does not induce place conditioning when animals are tested in a drug-free state, but does result in decreased locomotor activity and increased frequency thresholds for electrical self-stimulation of the ventral tegmental area (VTA). The present study was conducted to determine whether the 5-HT2C receptor agonist WAY 161503 may induce place conditioning in a state-dependent manner and also whether this compound will induce gustatory avoidance conditioning in the conditioned taste aversion (CTA) paradigm. The effects of the 5-HT2C receptor agonist WAY 161503 in the place conditioning and CTA (two-bottle choice test) paradigms were assessed in male Sprague-Dawley rats. Administration of WAY 161503 (3.0 mg/kg) induced a state-dependent conditioned place aversion and a CTA to saccharin. The differential state dependency of 5-HT2C receptor agonists' effects in place conditioning (state dependent) and CTA (non-state dependent) is consistent with the activation of different brain systems in these two paradigms. The state-dependent effects in place conditioning underscore the need to include controls for state dependency in studies of 5-HT receptor related compounds.
Mosher
T M
TM
W.G. Dewhurst Laboratory, Neurochemical Research Unit, Department of Psychiatry and Centre for Neuroscience, 1E7.44 WMHSC, University of Alberta, Edmonton, AB, T6G 2R7, Canada.
Smith
J G
JG
Greenshaw
A J
AJ
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005518:Food Preferences / Q000187:drug effects; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000187:drug effects; D012439:Saccharin / Q000494:pharmacology; D058826:Serotonin 5-HT2 Receptor Agonists; D013549:Sweetening Agents / Q000494:pharmacology; D013997:Time Factors
C502777:8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one; D018765:Dopamine Uptake Inhibitors; D011719:Pyrazines; D011810:Quinoxalines; D058826:Serotonin 5-HT2 Receptor Agonists; D013549:Sweetening Agents; D000661:Amphetamine; D012439:Saccharin