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Effect of a novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats

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Abstract

Rationale and objective

Recent work has shown that the novel compound N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB) may selectively block nicotinic acetylcholine receptors involved in regulating dopamine release. The current experiments examined the acute effect of bPiDDB on nicotine self-administration, sucrose-maintained responding, and nicotine-induced changes in acute and sensitized locomotor activity.

Methods

Rats were first trained to respond for either nicotine (i.v.) or sucrose pellets using a standard two-lever operant conditioning procedure using a fixed ratio 5 schedule of reinforcement and were then pretreated with bPiDDB (0, 0.3, 1, or 3 mg kg−1) 15 min prior to the session. In separate experiments, rats were assessed for nicotine-induced changes in locomotor activity following pretreatment with bPiDDB (1 or 3 mg kg−1) or mecamylamine (1 mg kg−1); pretreatments were assessed with both acute and repeated nicotine (0.4 mg kg−1) treatment.

Results

Results showed that bPiDDB dose-dependently decreased nicotine self-administration, but not sucrose-maintained responding. In the locomotor experiments, bPiDDB attenuated the hyperactivity produced by acute and repeated nicotine; however, this effect was not robust compared to mecamylamine. In contrast to mecamylamine, bPiDDB did not block the initial hypoactivity produced by acute nicotine.

Conclusion

Since bPiDDB decreased nicotine self-administration specifically, this novel nicotinic receptor antagonist may constitute a lead for the development of a clinically useful treatment for tobacco dependence.

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Acknowledgements

This work was supported by USPHS grant U19 DA17548 and by NIDA training grant T32 DA07304. We acknowledge the excellent technical assistance of Laura Fenton and Andrew Meyer and the expert advice of Dr. William Corrigall. For purposes of full disclosure, the University of Kentucky holds patents on bPiDDB, and a potential royalty stream to LPD and PAC may occur consistent with the University of Kentucky policy.

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Authors and Affiliations

  1. Department of Psychology, University of Kentucky, Lexington, KY, 40506, USA

    N. M. Neugebauer & M. T. Bardo

  2. College of Pharmacy, University of Kentucky, Lexington, KY, USA

    Z. Zhang, P. A. Crooks & L. P. Dwoskin

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  1. N. M. Neugebauer
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  2. Z. Zhang
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  3. P. A. Crooks
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  4. L. P. Dwoskin
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  5. M. T. Bardo
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Correspondence to M. T. Bardo.

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Neugebauer, N.M., Zhang, Z., Crooks, P.A. et al. Effect of a novel nicotinic receptor antagonist, N,N′-dodecane-1,12-diyl-bis-3-picolinium dibromide, on nicotine self-administration and hyperactivity in rats. Psychopharmacology 184, 426–434 (2006). https://doi.org/10.1007/s00213-005-0163-8

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  • DOI: https://doi.org/10.1007/s00213-005-0163-8

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