Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine self-administration in rats.

Journal Article (Journal Article)

Nicotine intake constitutes a principal mechanism for tobacco addiction. In addition to primary effects on nicotinic acetylcholine receptors, nicotine has cascading effects, which may also underlie its neurobehavioral actions. Nicotine induces serotonin (5-HT) release, which has not classically been thought to be involved in tobacco addiction as dopamine has. However, addiction can be characterized more as a disorder of compulsion than a disorder of enjoyment. 5-HT mechanisms play key roles in compulsive disorders. Nicotine-induced 5-HT release may be a key to tobacco addiction. Ketanserin, a 5-HT2a and 5-HT2c receptor antagonist, significantly attenuates nicotine effects on attention and memory. These studies were conducted to determine if ketanserin would reduce nicotine self-administration in rats. Male Sprague-Dawley rats (N=12) were given initial food pellet training and then 10 sessions of nicotine self-administration training (0.03 mg/kg/infusion, i.v.). Then the rats were administered ketanserin (1 or 2 mg/kg, s.c.) or the saline vehicle. Ketanserin (2 mg/kg) significantly decreased nicotine self-administration. This did not seem to be due to sedative or amnestic effects of ketanserin. In a second study, the effects of repeated administration of 2 mg/kg ketanserin (N=11) vs. saline injections (N=10) were examined. In the initial phase, the acute effectiveness of ketanserin in significantly reducing nicotine self-administration was replicated. The effect became attenuated during the following several sessions, but the significant effect became re-established during the final phases of this two-week study. 5-HT mechanisms play critical roles in the maintenance of nicotine self-administration. Better understanding of those roles may help lead to new 5-HT-based treatments for tobacco addiction.

Full Text

Duke Authors

Cited Authors

  • Levin, ED; Slade, S; Johnson, M; Petro, A; Horton, K; Williams, P; Rezvani, AH; Rose, JE

Published Date

  • December 14, 2008

Published In

Volume / Issue

  • 600 / 1-3

Start / End Page

  • 93 - 97

PubMed ID

  • 18950618

Pubmed Central ID

  • PMC2638587

Electronic International Standard Serial Number (EISSN)

  • 1879-0712

Digital Object Identifier (DOI)

  • 10.1016/j.ejphar.2008.10.016


  • eng

Conference Location

  • Netherlands