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Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin.

Publication ,  Journal Article
DiPalma, D; Rezvani, AH; Willette, B; Wells, C; Slade, S; Hall, BJ; Levin, ED
Published in: Pharmacol Biochem Behav
January 2019

Tobacco addiction each year causes millions of deaths worldwide. Brain nicotinic acetylcholine receptors have been shown to be central to tobacco addiction. Nicotine replacement therapy aids tobacco cessation, but the success rate is still far too low. This may in part be due to the fact that neurons with nicotinic receptors are not the only neural systems involved in tobacco addiction. Interacting neural systems also play important roles in tobacco addiction. Nicotine increases the release of a variety of neurotransmitters, including dopamine and serotonin. Dopamine, in particular dopamine D1 receptors, has been shown to be involved in the reinforcing action of nicotine. Serotonin through its actions on 5-HT2C receptors has been shown to play a key role in modulating the reinforcement of addictive drugs, including nicotine and alcohol. Combination of treatments could provide greater treatment efficacy. These studies were conducted to evaluate combination therapies utilizing nicotine replacement therapy in conjunction with either a dopamine D1 receptor antagonist SCH-23390 or a serotonin 5-HT2C receptor agonist, lorcaserin. Female Sprague-Dawley rats were given access to self-administer nicotine via IV infusions. Osmotic pumps were implanted to reproduce the kinetic of chronic nicotine patch therapy. SCH-23390 (0.02 mg/kg) or lorcaserin (0.6 mg/kg) were administered prior to nicotine self-administration sessions. Reproducing earlier findings SCH-23390, lorcaserin and nicotine replacement therapy were effective at reducing IV nicotine self-administration. 5HT2C agonist treatment had additive effects with chronic nicotine infusion for significantly lowering nicotine self-administration. This study demonstrates the feasibility of combination of chronic nicotine with therapies targeting non-nicotinic receptors as treatment options for tobacco addiction.

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Published In

Pharmacol Biochem Behav

DOI

EISSN

1873-5177

Publication Date

January 2019

Volume

176

Start / End Page

16 / 22

Location

United States

Related Subject Headings

  • Tobacco Use Disorder
  • Tobacco Use Cessation Devices
  • Smoking Cessation
  • Serotonin 5-HT2 Receptor Agonists
  • Self Administration
  • Receptors, Dopamine D1
  • Rats, Sprague-Dawley
  • Rats
  • Nicotine
  • Neurology & Neurosurgery
 

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DiPalma, D., Rezvani, A. H., Willette, B., Wells, C., Slade, S., Hall, B. J., & Levin, E. D. (2019). Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin. Pharmacol Biochem Behav, 176, 16–22. https://doi.org/10.1016/j.pbb.2018.11.002
DiPalma, Devon, Amir H. Rezvani, Blair Willette, Corinne Wells, Susan Slade, Brandon J. Hall, and Edward D. Levin. “Persistent attenuation of nicotine self-administration in rats by co-administration of chronic nicotine infusion with the dopamine D1 receptor antagonist SCH-23390 or the serotonin 5-HT2C agonist lorcaserin.Pharmacol Biochem Behav 176 (January 2019): 16–22. https://doi.org/10.1016/j.pbb.2018.11.002.
Journal cover image

Published In

Pharmacol Biochem Behav

DOI

EISSN

1873-5177

Publication Date

January 2019

Volume

176

Start / End Page

16 / 22

Location

United States

Related Subject Headings

  • Tobacco Use Disorder
  • Tobacco Use Cessation Devices
  • Smoking Cessation
  • Serotonin 5-HT2 Receptor Agonists
  • Self Administration
  • Receptors, Dopamine D1
  • Rats, Sprague-Dawley
  • Rats
  • Nicotine
  • Neurology & Neurosurgery