Brain regions mediating alpha 3 beta 4 nicotinic antagonist effects of 18-MC on nicotine self-administration

作者：Glick Stanley D^*; Sell Elizabeth M; McCallum Sarah E; Maisonneuve Isabelle M

来源：European Journal of Pharmacology, 2011, 669(1-3): 71-75.

DOI：10.1016/j.ejphar.2011.08.001

• 18-Methoxycoronaridine
• alpha-Conotoxin AuIB
• Mecamylamine
• Nicotine
• Medial habenula
• Interpeduncular nucleus
• Basolateral amygdala
• Ventral tegmental area
• Dorsolateral tegmentum
• alpha 3 beta 4 nicotinic receptors
• Drug self-administration
• Drug addiction

18-Methoxycoronaridine (18-MC), a putative anti-addictive agent, has been shown to decrease the self-administration of several drugs of abuse in rats. 18-MC is a potent antagonist at alpha 3 beta 4 nicotinic receptors. Consistent with high densities of alpha 3 beta 4 nicotinic receptors being located in the medial habenula and the interpeduncular nucleus, 18-MC has been shown to act in these regions to decrease both morphine and methamphetamine self-administration. The present study was conducted to determine if 18-MC's effect on nicotine self-administration is mediated by acting in these same brain regions. Because moderate densities of alpha 3 beta 4 receptors occur in the dorsolateral tegmentum, ventral tegmental area, and basolateral amygdala, these brain areas were also examined as potential sites of action of 18-MC. Local administration of 18-MC into either the medial habenula, the basolateral amygdala or the dorsolateral tegmentum decreased nicotine self-administration. Surprisingly, local administration of 18-MC into the interpeduncular nucleus increased nicotine self-administration while local administration of 18-MC into the ventral tegmental area had no effect on nicotine self-administration. Similar effects were produced by local administration of either mecamylamine or conotoxin AuIB. These data are consistent with the hypothesis that 18-MC decreases nicotine self-administration by indirectly modulating the dopaminergic mesolimbic pathway via blockade of alpha 3 beta 4 nicotinic receptors in the medial habenula, basolateral amygdala, and dorsolateral tegmentum. The data also suggest that an action of 18-MC in the interpeduncular nucleus may attenuate aversive and/or depressive effects of nicotine.

• 出版日期2011-11-1