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Behav Brain Res. 2016 Jul 1;307:186-93. doi: 10.1016/j.bbr.2016.04.008. Epub 2016 Apr 6.

18-Methoxycoronaridine acts in the medial habenula to attenuate behavioral and neurochemical sensitization to nicotine.

Author information

1
Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208, United States. Electronic address: Egganb@mail.amc.edu.
2
Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY 12208, United States. Electronic address: Mccalls@mail.amc.edu.

Abstract

Systemic 18-methoxycoronaridine, an alpha3beta4 nicotinic antagonist, slows the rate of induction of behavioral sensitization to nicotine (Glick et al., 1996; 2011). The primary mechanism of action of 18-MC is believed to be the inhibition of α3β4 nicotinic acetylcholine receptors which are densely expressed in the medial habenula and interpeduncular nucleus (Pace et al., 2004; Glick et al., 2012). Recently, these habenular nicotinic receptors and their multiple roles in nicotine aversion and withdrawal have been increasingly emphasized (Antolin-Fontes et al., 2015). Here, we investigated the effects of 18-MC on both behavioral and neurochemical sensitization to nicotine. Daily systemic administration of 18-MC slowed the rate of induction of behavioral sensitization to nicotine but failed to block the expression of a sensitized locomotor response when absent. In contrast, in nicotine sensitized animals, systemic 18-MC significantly reduced the expression of behavioral sensitization. Results from intra-habenular administration of 18-MC paralleled these findings in that the expression of behavioral sensitization was also reduced in sensitized animals. Consistent with its effects on behavioral sensitization, intra-MHb treatment with 18-MC completely abolished sensitized dopamine responses in the nucleus accumbens in nicotine sensitized animals. These results show that α3β4 nicotinic receptors in the MHb contribute to nicotine sensitization, a phenomenon associated with drug craving and relapse.

KEYWORDS:

18-Methoxycoronaridine; Locomotor activity; Medial habenula; Microdialysis; Nicotine; Rat; Sensitization; α3β4 nicotinic acetylcholine receptors

PMID:
27059333
DOI:
10.1016/j.bbr.2016.04.008
[Indexed for MEDLINE]

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