Effect of the 5-HT(6) serotonin antagonist MS-245 on the actions of (-)nicotine

Pharmacol Biochem Behav. 2006 Sep;85(1):170-7. doi: 10.1016/j.pbb.2006.07.029. Epub 2006 Sep 6.

Abstract

The 5-HT(6) serotonin receptor antagonist MS-245 neither substitutes for nor antagonizes the discriminative stimulus effects of (-)nicotine. However, MS-245 was shown to enhance the potency of (-)nicotine in Sprague-Dawley rats trained to discriminate 0.6 mg/kg of (-)nicotine from saline vehicle in a typical two-lever drug discrimination paradigm such that a combination of MS-245 (5.0 mg/kg) plus the ED(50) dose of (-)nicotine caused the animals to respond as if they had received the training dose of (-)nicotine. MS-245 also potentiated the hypolocomotor actions, but not the antinociceptive effects, of (-)nicotine in mice. The results suggest possible involvement of serotonin-regulated signaling mechanisms in certain behavioral effects of nicotine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Nicotine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Tryptamines / pharmacology*

Substances

  • N1-benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine
  • Receptors, Serotonin
  • Tryptamines
  • serotonin 6 receptor
  • Nicotine