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Role of the β4 nicotinic receptor subunit in the anti‐addictive activity of 18‐methoxycoronaridine
Author(s) -
Mukhida Samir,
Arias Hugo R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.762.4
Subject(s) - addiction , sensitization , pharmacology , nicotinic agonist , nicotinic acetylcholine receptor , protein subunit , acetylcholine receptor , nicotine , locomotor activity , drug , chemistry , mutant , receptor , psychology , biology , neuroscience , biochemistry , gene
The ibogaine analog 18‐methoxycoronaridine (18‐MC) is known to reduce the self‐administration of several addictive drugs. It is proposed that this anti‐addictive activity is mediated by the noncompetitive inhibition of β4 nicotinic acetylcholine receptors (AChRs) expressed in the habenulo‐interpeduncular pathway, a brain reward circuit that is known to contribute to the process of drug addiction. To test this, we studied the role of the β4 nicotinic subunit in the process of drug addiction and in the anti‐addictive activity of 18‐MC by using forced swim tests on mutant mice. We first compared the results between cocaine and saline treatments between wild type (β4+/+) and mutant (β4−/−) male and female mice, and subsequently determined the anti‐addictive effect of 18‐ MC on cocaine‐induced locomotor sensitization between wild type and mutant mice from both sexes. The results indicate that the presence of the β4 subunit in males causes a lower cocaine induced total locomotor activity, but higher peak sensitization. Female mice expressing the β4 subunit have a higher peak activity 15 min after cocaine injections compared to male mice, indicating that the anti‐addictive effect of 18‐MC is more pronounced in male mice. In conclusion, the presence of the β4 subunit increases the anti‐cocaine effect of 18‐MC, confirming its modulatory role in drug addiction and the potential therapeutic relevance of the β4 subunit.