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Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

Publication ,  Journal Article
Briggs, SA; Hall, BJ; Wells, C; Slade, S; Jaskowski, P; Morrison, M; Rezvani, AH; Rose, JE; Levin, ED
Published in: Pharmacol Biochem Behav
March 2016

Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self-administration replicating previous findings. Augmenting interactions were observed with dextromethorphan and pyrilamine as well as lorcaserin. These findings suggest that combination therapy may be more effective smoking cessation treatments than monotherapy.

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Published In

Pharmacol Biochem Behav

DOI

EISSN

1873-5177

Publication Date

March 2016

Volume

142

Start / End Page

1 / 7

Location

United States

Related Subject Headings

  • Serotonin Receptor Agonists
  • Self Administration
  • Rats, Sprague-Dawley
  • Rats
  • Pyrilamine
  • Nicotine
  • Neurology & Neurosurgery
  • Histamine H1 Antagonists
  • Female
  • Dextromethorphan
 

Citation

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Briggs, S. A., Hall, B. J., Wells, C., Slade, S., Jaskowski, P., Morrison, M., … Levin, E. D. (2016). Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav, 142, 1–7. https://doi.org/10.1016/j.pbb.2015.12.004
Briggs, Scott A., Brandon J. Hall, Corinne Wells, Susan Slade, Paul Jaskowski, Margaret Morrison, Amir H. Rezvani, Jed E. Rose, and Edward D. Levin. “Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.Pharmacol Biochem Behav 142 (March 2016): 1–7. https://doi.org/10.1016/j.pbb.2015.12.004.
Briggs SA, Hall BJ, Wells C, Slade S, Jaskowski P, Morrison M, et al. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav. 2016 Mar;142:1–7.
Briggs, Scott A., et al. “Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.Pharmacol Biochem Behav, vol. 142, Mar. 2016, pp. 1–7. Pubmed, doi:10.1016/j.pbb.2015.12.004.
Briggs SA, Hall BJ, Wells C, Slade S, Jaskowski P, Morrison M, Rezvani AH, Rose JE, Levin ED. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav. 2016 Mar;142:1–7.
Journal cover image

Published In

Pharmacol Biochem Behav

DOI

EISSN

1873-5177

Publication Date

March 2016

Volume

142

Start / End Page

1 / 7

Location

United States

Related Subject Headings

  • Serotonin Receptor Agonists
  • Self Administration
  • Rats, Sprague-Dawley
  • Rats
  • Pyrilamine
  • Nicotine
  • Neurology & Neurosurgery
  • Histamine H1 Antagonists
  • Female
  • Dextromethorphan