Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine-induced place conditioning and locomotor activity in rats.
BACKGROUND
Numerous studies indicate a role for both the serotonin 2C receptor (5-HT(2C)) and the nicotinic acetylcholine receptor in locomotion, reinforcement and motivated behaviours. Nicotine, a potent nicotinic acetylcholine receptor agonist, interacts with the dopaminergic and serotonergic systems and is known to positively affect reward-related behaviours.


OBJECTIVE
The current study examined the effects of 5-HT(2C) receptor activation on nicotine-induced (0.6 mg/kg) place conditioning and spontaneous locomotion.


METHODS
Using Sprague-Dawley rats, the effects of the selective 5-HT(2C) receptor agonist WAY 161503 (0-1.0 mg/kg) and the selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) alone, in combination, and on nicotine-induced (0.6 mg/kg) spontaneous locomotor activity were assessed. The effects of WAY 161503 (1.0, 3.0 mg/kg) were also investigated in nicotine-induced place conditioning using a two-compartment biased design; amphetamine (1.0 mg/kg) served as a positive control. As differential effects were observed between place conditioning and locomotor activity, the subjects used in the place conditioning experiments were also tested for effects on locomotor activity.


RESULTS
WAY 161503 decreased baseline and nicotine-induced locomotor activity at the highest dose tested (1.0mg/kg) and these effects were attenuated by SB 242084. Amphetamine and nicotine both induced robust place preferences and WAY 161503 did not have any effects in the context of place conditioning. In contrast, WAY 161503 (1.0 mg/kg) blocked nicotine-induced locomotor activity.


CONCLUSIONS
These results suggest that 5-HT(2C) receptors may play an inhibitory role in nicotine-induced locomotor activity, but do not appear to influence place conditioning under the current conditions.
Hayes
Dave J
DJ
Centre for Neuroscience, 513 HMRC, University of Alberta, Edmonton, AB T6G 2S2, Canada. dave.hayes@ualberta.ca
Mosher
Tera M
TM
Greenshaw
Andrew J
AJ
D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012201:Reward; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists
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; D015259:Dopamine Agents; D007211:Indoles; D018722:Nicotinic Agonists; D011719:Pyrazines; D011810:Quinoxalines; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D009538:Nicotine; D000661:Amphetamine