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Hypocretins May Contribute to Nicotine Addiction

Blocking hypocretin transmission may regulate the reinforcing effects of nicotine

WEDNESDAY, Nov. 26 (HealthDay News) -- Hypocretins of the insular cortex may play a key role in the neurobiological mechanism underlying nicotine addiction, according to research published online Nov. 24 in the Proceedings of the National Academy of Sciences.

Jonathan A. Hollander, Ph.D., of Molecular Therapeutics in Jupiter, Fla., and colleagues investigated the role of hypocretin transmission at Hcrt-1 receptors in regulating nicotine consumption and motivation to obtain the substance, using male Wistar rats. The investigators tested the effects of systemically delivered (into insula) selective Hcrt-1 receptor antagonist SB-334867 on response to nicotine or food rewards, using different (fixed or progressive ratio) reinforcement schedules.

The findings suggest that insular hypocretin transmission may be a key substrate regulating the reinforcing effects of nicotine as experimentally observed with dose-dependent decrease in nicotine self-administration in response to Hcrt-1 receptor antagonist SB-334867. At the highest dose of SB-334867 (5 μg/side; 15.6 nmol/side) infusion into the insular cortex, nicotine intake was reduced by approximately 60 percent.

"Collectively, our findings demonstrate that hypocretin transmission at Hcrt-1 receptors in the insular cortex is a critical target necessary for the expression of the motivational properties of nicotine. Hence, destruction of insular hypocretin transmission in smokers who suffer damage to this brain region may explain the profound disruption of tobacco addiction observed in these individuals," the authors conclude.

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