Influence of the 5-HT2C receptor antagonist, SB-242084, in tests of anxiety

Pharmacol Biochem Behav. 2002 Apr;71(4):615-25. doi: 10.1016/s0091-3057(01)00713-4.

Abstract

The 5-HT2C antagonist SB-242084 was examined in various anxiety tests at doses based on reversal of mCPP-induced hypoactivity (0.1--3 mg/kg ip). In the elevated plus-maze task, SB-242084 exhibited signs of anxiolysis (time spent, distance travelled, and entries into open arms), but this was potentially confounded by its general increase of locomotion; alprazolam selectively affected open-arm parameters. In a Geller--Seifter conflict test, SB-242084 produced a modest, nonsignificant increase in punished responding compared to the significant effect produced by diazepam. None of the treatments significantly affected unpunished responding. In the conditioned emotional response (CER) test, SB-242084 produced an increase in the suppression ratio (SR, smaller than diazepam). Since this 5-HT2C antagonist also increased lever pressing, an additional test was conducted with amphetamine that stimulated lever pressing but, nonetheless, failed to produce any change in SR. In the fear-potentiated startle task, SB-242084 was inactive in comparison to a significant effect of diazepam. The previously described reduction of schedule-induced polydipsia by fluoxetine and 5-HT2C receptor agonist Ro60-0175 was attenuated by SB-242084 pretreatment, however, the latter compound exhibited a potent increase in polydipsia when given alone. The present results demonstrate an anxiolytic potential of SB-242084, as well as an intrinsic response-enhancing property, however, both of these effects are task dependent.

MeSH terms

  • Aminopyridines / pharmacology*
  • Animals
  • Anxiety / psychology*
  • Compulsive Behavior / psychology
  • Conditioning, Operant / drug effects
  • Conflict, Psychological
  • Diazepam / pharmacology
  • Dose-Response Relationship, Drug
  • Drinking / drug effects
  • Emotions / drug effects
  • Fear / drug effects
  • GABA Modulators / pharmacology
  • Indoles / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects*
  • Reflex, Startle / drug effects
  • Reinforcement Schedule
  • Serotonin Antagonists / pharmacology*
  • Taste / drug effects

Substances

  • 6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline
  • Aminopyridines
  • GABA Modulators
  • Indoles
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Diazepam