Differential effects of 5-HT2C receptor ligands on place conditioning and locomotor activity in rats

Eur J Pharmacol. 2005 May 16;515(1-3):107-16. doi: 10.1016/j.ejphar.2005.03.041.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopyridines / pharmacology
  • Animals
  • Conditioning, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Indoles / pharmacology
  • Ligands
  • Male
  • Motor Activity / drug effects*
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Pyrazines / pharmacology
  • Pyridines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1A / physiology
  • Receptor, Serotonin, 5-HT1B / physiology
  • Receptor, Serotonin, 5-HT2C / physiology*
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists / pharmacology
  • Time Factors

Substances

  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • 8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one
  • Aminopyridines
  • Indoles
  • Ligands
  • Oxadiazoles
  • Piperazines
  • Pyrazines
  • Pyridines
  • Quinoxalines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin 5-HT2 Receptor Agonists
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • 1-(3-trifluoromethylphenyl)piperazine
  • GR 127935
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide