Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats

J Pharmacol Exp Ther. 2011 Sep;338(3):890-6. doi: 10.1124/jpet.111.183525. Epub 2011 Jun 2.

Abstract

Lorcaserin, a selective 5-hydroxytryptamine(2C) (5-HT(2C)) agonist, has been shown to facilitate weight loss in obese populations. It was assessed for its efficacy in reducing nicotine self-administration in young adult female Sprague-Dawley rats. The effect of short-term doses (subcutaneous) on nicotine self-administration (0.03 mg/kg per infusion) with a fixed ratio 1 schedule was assessed in 3-h sessions. Short-term lorcaserin doses (0.3125-20 mg/kg) were administered in a counterbalanced order. Significant reduction of nicotine self-administration was achieved with all of the short-term doses in this range. Tests of lorcaserin on locomotor activity detected prominent sedative effects at doses greater than 1.25 mg/kg with more modest transient effects seen at 0.625 to 1.25 mg/kg. Long-term effects of lorcaserin on locomotor activity were tested with repeated injections with 0.625 mg/kg lorcaserin 10 times over 2 weeks. This low lorcaserin dose did not cause an overall change in locomotor activity relative to that of saline-injected controls. Long-term lorcaserin (0.625 mg/kg) significantly reduced nicotine self-administration over a 2-week period of repeated injections. Long-term lorcaserin at this same dose had no significant effects on food self-administration over the same 2-week period of repeated injections. These studies support development of the 5-HT(2C) agonist lorcaserin to aid tobacco smoking cessation.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Benzazepines / administration & dosage
  • Benzazepines / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Food
  • Motivation
  • Motor Activity / drug effects
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C / drug effects*
  • Reward
  • Self Administration
  • Serotonin 5-HT2 Receptor Agonists / administration & dosage
  • Serotonin 5-HT2 Receptor Agonists / pharmacology*
  • Smoking Cessation
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / psychology*

Substances

  • Benzazepines
  • Nicotinic Agonists
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • lorcaserin
  • Nicotine