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Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats

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Abstract

Rationale

Chronic nicotine infusion via transdermal patches has been widely shown to assist with smoking cessation. In particular, transdermal nicotine treatment prior to quitting smoking helps reduce ad libitum smoking and aids cessation Rose et al. (Nicotine Tob Res 11:1067–75, 2009). However, despite this success, the majority of smokers who use transdermal nicotine fail to permanently quit smoking. Additional treatments are needed. Tobacco addiction does not just depend on nicotinic receptor systems; a variety of neural systems are involved, including dopamine, norepinepherine, serotonin, and histamine.

Objectives

Given the involvement of a variety of neural systems in the circuits of addiction, combination therapy may offer improved efficacy for successful smoking cessation beyond single treatments alone. We have found that pyrilamine, an H1 histamine antagonist, significantly decreases nicotine self-administration in rats.

Methods

The current study was conducted to confirm the effect of chronic nicotine infusion on ongoing nicotine self-administration and resumed access after enforced abstinence and to determine the interaction of chronic nicotine with an H1 antagonist treatment.

Results

Chronic nicotine infusion via osmotic minipump (2.5 and 5 mg/kg/day for 28 days) significantly reduced nicotine self-administration in a dose-dependent manner. Chronic nicotine infusion also reduced the resumption of nicotine self-administration after enforced abstinence. Chronic pyrilamine infusion (25 mg/kg/day for 14 days) also significantly reduced nicotine self-administration.

Conclusion

The combination of chronic nicotine and pyrilamine reduced nicotine self-administration to a greater extent than treatment with either drug alone.

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Acknowledgments

This research was supported by P50 grant DA027840 from NIDA.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Box 104790, Durham, NC, 27710, USA

    Edward D. Levin, Brandon J. Hall, Autri Chattopadhyay, Susan Slade, Corinne Wells, Amir H. Rezvani & Jed E. Rose

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  1. Edward D. Levin
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  2. Brandon J. Hall
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  3. Autri Chattopadhyay
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  4. Susan Slade
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  5. Corinne Wells
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  6. Amir H. Rezvani
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  7. Jed E. Rose
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Correspondence to Edward D. Levin.

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Levin, E.D., Hall, B.J., Chattopadhyay, A. et al. Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats. Psychopharmacology 233, 3009–3015 (2016). https://doi.org/10.1007/s00213-016-4347-1

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  • DOI: https://doi.org/10.1007/s00213-016-4347-1

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