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Mu‐opioid receptors are involved in the tolerance to nicotine antinociception
Author(s) -
Galeote Lola,
Kieffer Brigitte L.,
Maldonado Rafael,
Berrendero Fernando
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03751.x
Subject(s) - damgo , nicotine , chemistry , opioid , pharmacology , μ opioid receptor , receptor , medicine , endocrinology , enkephalin , biochemistry
Several studies have shown the participation of the endogenous opioid system on the antinociceptive effects and addictive properties of nicotine. The aim of the present study was to explore the involvement of the mu‐opioid receptors in the development of tolerance to nicotine antinociception. Chronic treatment of C57BL/6 mice with nicotine (5 mg/kg s.c., three times daily during 12 days) resulted in tolerance to its antinociceptive responses in the tail‐immersion test. We investigated the possible existence of adaptive changes in the expression and/or functional activity of mu‐opioid receptors in these tolerant mice by using autoradiography of [ 3 H] d ‐Ala 2 ‐MePhe 4 ‐Gly‐ol 5 enkephalin ([ 3 H]DAMGO) binding and DAMGO‐stimulated guanosine [ 35 S]5′‐(γ‐thio)‐triphosphate ([ 35 S]GTPγS) binding. The density of mu‐opioid receptors in the spinal cord was not modified in nicotine‐tolerant mice, whereas a decrease was found in the caudate‐putamen, as well as in the core and the shell of the nucleus accumbens. However, the functional activity of these receptors was significantly increased in the spinal cord as a consequence of nicotine treatment. To further investigate the role of mu‐opioid receptors in the tolerance to nicotine‐induced antinociception, we evaluated this response in C57BL/6 mu‐opioid receptor knockout mice. Chronic nicotine treatment produced tolerance in both wild‐type and knockout animals, but tolerance developed faster in mice lacking mu‐opioid receptors. These results indicate that mu‐opioid receptors play an important role in the development of tolerance to nicotine antinociceptive effects.