Abstract
Nicotine (i.e. tobacco) and morphine are among the most widely consumed drugs in humans. Recent evidence has suggested the existence of common pathways in the mechanisms of action of nicotine and opioid receptor agonists. This paper reviews research of functional interactions between nicotine and morphine in the modulation of behavioral responses in animal paradigms, especially in antinociception and addiction-related processes.
References
1. A r a k i H., K a w a k a m i K. Y., Jin C. et al.: Nicotine attenuates place aversion induced by
naloxone in single-dose, morphine-treated rats. Psychopharmacology, 17, 398, 2004.
2. B e r r e n d e r o F., K i e f f e r B. L., M a l d o n a d o R.: Attenuation of nicotine-induced
antinociception, rewarding effects, and dependence in μ-opioid receptor knock-out mice. J.
Neurosci, 22, 10935, 2002.
3. B i a l a G., B u d z y n s k a B., S t a n i a k N.: Effects of rimonabant on the reinstatement
of nicotine-conditioned place preference by drug priming in rats. Behav Brain Res., 2009,
doi:10.1016/j.bbr.2009.03.042
4. B i a l a G., B u d z y n s k a B., K r u k M.: Naloxone precipitates nicotine abstinence syndrome
and attenuates nicotine-induced antinociception in mice. Pharmacol. Rep., 57, 755, 2005.
5. B i a l a G., W e g l i n s k a B.: Calcium channel antagonists attenuate cross-sensitization to the
rewarding and/or locomotor effects of nicotine, morphine and MK-801. J Pharm Pharmacol., 56,
1021, 2004.
6. B i a l a G., W e g l i n s k a B.: On the mechanism of cross-tolerance between morphine- and
nicotine-induced antinociception: Involvement of calcium channels. Prog Neuropsychopharmacol.
Biol. Psychiatry, 30, 15, 2006.
7. B u d z y ń s k a B., B i a ł a G.: Reinstatement of drug addiction in animal models. Annales
UMCS, sect. DDD, vol. XIX, N 2, 89, 2006.
8. C a m p b e l l V. C., T a y l o r R. E., T i z a b i Y.: Antinociceptive effects of alcohol and nicotine:
involvement of the opioid system. Brain Res, 1097, 71, 2006.
9. C o r d e r o - E r a u s q u i n M., C h a n g e u x J. P.: Tonic nicotinic modulation of serotoninergic
transmission in the spinal cord, Proc. Natl. Acad. Sci. USA, 98, 2803, 2001.
10. D a v e n p o r t K. E., H o u d i A. A., V a n L o o n G. R.: Nicotine protects against mu-
opioid receptor antagonism by beta-funaltrexamine: evidence for nicotine-induced release of
endogenous opioids in brain. Neurosci. Lett., 113, 40, 1990.
11. D i C h i a r a G.: Role of dopamine in behavioural actions of nicotine related to addiction. Eur.
J. Pharmacol., 393, 295, 2000.
12. D i C h i a r a G., I m p e r a t o A.: Drugs abused by humans preferentially increase synaptic
dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Nat. Acad. Sci.
USA, 85, 5274, 1988.
13. F i s e r o v a M., C o n s o l o S., K r s i a k M.: Chronic morphine induces long-lasting changes
in acetylcholine release in rat nucleus accumbens core and shell: an in vivo microdialysis study.
Psychopharmacology, 142, 85, 1999.
14. H i l d e b r a n d B. E., N o m i k o s G. G., H e r t e l P. et al.: Reduced dopamine output in the
nucleus accumbens but not in the medial prefrontal cortex in rats display a mecamylamine-
precipitated nicotine withdrawal syndrome. Brain Res., 779, 214, 1998.
15. H o u d i A. A., P i e r z c h a l a K., M a r s o n L. et al.: Nicotine-induced alteration in Tyr-
Gly-Gly and Met-enkephalin in discrete brain nuclei reflects altered enkephalin neuron activity.
Peptides, 12, 161, 1991.
16. K i g u c h i N., M a e d a T., T s u r u g a M. et al.: Involvement of spinal Met-enkephalin in
nicotine-induced antinociception in mice. Brain Res., 1189, 70, 2008.
17. K l i t e n i c k M. A., D e W i t t e P., K a l i v a s P. W.: Regulation of somatodendric dopamine
release in the ventral tegmental area by opioids and GABA: an in vivo microdialysis study. J.
Neurosci., 12, 2623, 1992.
18. L i X., E i s e n a c h J. C.: Nicotinic acetylcholine receptor regulation of spinal norepinephrine
release. Anesthesiology, 96, 1450, 2002.
19. M a l i n D. H.: Nicotine dependence. Studies with a laboratory model. Pharmacol. Biochem.
Behav., 70, 551, 2001.
20. M a l i n D. H., L a k e J. R., N e w l i n - M a u l t s b y P. et al.: Rodent model of nicotine
abstinence syndrome. Pharmacol. Biochem. Behav., 43, 779, 1992.
21. M a n s o u r A., F o x C. A., A k i l H. et al.: Opioid-receptor mRNA expression in the rat CNS:
anatomical and functional implications. Trends Neurosci., 18, 22, 1995.
22. M i l l e r A. D., B l a h a C. D.: Midbrain muscarinic receptor mechanisms underlying regulation
of mesoaccumbens and nigrostriatal dopaminergic transmission in the rat Eur. J. Neurosci., 21,
1837, 2005.
23. P o l a s t r o n J., M e u n i e r J. C., J a u z a c P.: Chronic morphine induces tolerance and
desensitization of μ-opioid receptor but not down-regulation in rabbit. Eur. J. Pharmacol., 266,
139, 1994.
24. P o m e r l e a u O. F.: Endogenous opioids and smoking: a review of progress and problems.
Psychoneuroendocrinology., 23, 115, 1998.
25. R e z a y o f A., Z a t a l i H., H a e r i - R o h a n i A. et al.: Dorsal hippocampal muscarinic and
nicotinic receptors are involved in mediating morphine reward. Behav. Brain Res., 166, 281,
2006.
26. S c h n o l l R. A., L e r m a n C.: Current and emerging pharmacotherapies for treating tobacco
dependence. Expert Opin. Emerg. Drugs, 11, 429, 2006.
27. S i m o n s C. T., C u e l l a r J. M., M o o r e J. A. et al.: Nicotinic receptor involvement in
antinociception induced by exposure to cigarette smoke. Neurosci. Lett., 389, 71, 2005.
28. T o m e A. R., I z a g u i r r e V., R o s a r i o L. M. et al.: Naloxone inhibits nicotine-induced
receptor current and catecholamine secretion in bovine chromaffin cells. Brain Res., 903, 62,
2001.
29. V i h a v a i n e n T., R e l a n d e r T. R., L e i v i s k ä R. et al.: Chronic nicotine modifies
the effects of morphine on extracellular striatal dopamine and ventral tegmental GABA. J
Neurochem., 107, 844, 2008.
30. W e w e r s M. E., D h a t t R. K., S n i v e l y T. A. et al.: The effect of chronic administration
of nicotine on antinociception, opioid receptor binding and met-enkephalin levels in rats. Brain
Res., 822, 107, 1999.
31. W o n n a c o t t S.: Presynaptic nicotinic ACh receptors. Trends Neurosci., 20, 92, 1997.
32. Y e o m a n s J., B a p t i s t a M.: Both nicotinic and muscarinic receptors in ventral tegmental
area contribute to brain-stimulation reward. Pharmacol. Biochem. Behav., 57, 915, 1997.
33. Z a r r i n d a s t M. R., F a r z i n D.: Nicotine attenuates naloxone-induced jumping behaviour
in morphine-dependent mice. Eur. J. Pharmacol., 298, 1, 1996.
34. Z a r r i n d a s t M. R., K h o s h a y a n d M. R., Shafaghi B.: The development of cross-tolerance
between morphine and nicotine in mice. Eur. Neuropsychopharmacol., 9, 227, 1999.

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
Copyright (c) 2009 Author