A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats

Behav Brain Res. 2013 Jan 1;236(1):157-165. doi: 10.1016/j.bbr.2012.08.048. Epub 2012 Sep 4.

Abstract

Recent studies suggest a potential role for 5-hydroxytryptamine(6) (5-HT(6)) receptors in the regulation of addictive behavior. In the present study, our aim was to investigate whether the novel highly selective 5-HT(6) receptor antagonist compound (CMP) 42 affected nicotine and ethanol seeking behavior in Wistar rats. We have also studied whether CMP 42 had beneficial effects in a model of impulse control, as measured in the 5-choice serial reaction time task (5-CSRTT). Rats were trained to nose poke to receive intravenous infusions of nicotine or an ethanol drop. CMP 42 (3-30 mg/kg intraperitoneally, i.p.) was administered to investigate the effects on nicotine self-administration. Rats were also tested for cue-induced reinstatement of nicotine and ethanol seeking. In addition, the effects of CMP 42 were studied on the number of anticipatory responses in the 5-CSRTT. CMP 42 was effective in reducing nicotine self-administration and reinstatement of nicotine seeking at a dose of 30 mg/kg (i.p.). CMP 42 was also effective in reducing reinstatement of ethanol seeking (30 mg/kg i.p.). In contrast, CMP 42 did not affect anticipatory responding at doses tested, indicating no effects on impulse control. These results add to a body of evidence implicating the 5-HT(6) receptor as a viable target for the control of drug abuse. Specifically, we demonstrated for the first time effects on nicotine self-administration and on nicotine and ethanol reinstatement. Further, these effects are probably not mediated by effects on impulse control.

MeSH terms

  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / psychology
  • Analysis of Variance
  • Animals
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology
  • Cues
  • Data Interpretation, Statistical
  • Drug-Seeking Behavior / drug effects*
  • Ethanol / administration & dosage
  • Ethanol / pharmacology
  • Extinction, Psychological / drug effects
  • Impulsive Behavior / drug therapy
  • Impulsive Behavior / psychology
  • Infusions, Intravenous
  • Male
  • Nicotine / administration & dosage
  • Nicotine / pharmacology
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Receptors, Serotonin / drug effects*
  • Recurrence
  • Self Administration
  • Serotonin Antagonists / pharmacology*
  • Sulfonamides / pharmacology
  • Tobacco Use Disorder / drug therapy*
  • Tobacco Use Disorder / psychology

Substances

  • CMP 42
  • Central Nervous System Depressants
  • Nicotinic Agonists
  • Pyrazoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • serotonin 6 receptor
  • Ethanol
  • Nicotine