Aim: 

The mesostriatal DA pathway is a major brain target for nicotinic agonists and mediates several of their behavioural effects including their addictive properties. The purpose of this paper is to examine the functional role of alpha6* nAChRs, a subtype that is highly and selectively enriched in DA neurons.

Methods: 

Adult male Sprague-Dawley rats were used. Alpha-conotoxin (Cntx) MII and PIA, alpha6beta2* selective antagonists, were infused through microdialysis cannulas placed in the ventral tegmental area (VTA) and the animals tested in different experimental paradigms including intracerebral microdialysis for DA and habituated locomotion. Nicotine was administered i.p. at the dose of 0.4 mg/kg.

Results: 

While infusion of CntxMII in the n. accumbens (nAc) did not significantly modify nicotine-elicited release of DA in the nAc, infusion of either CntxMII (10 or 1 mM, but not 100 nM) or CntxPIA (100 or 10 mM) into the VTA completely abolished nicotine effects. At the same doses, bilateral infusion of CntxMII or CntxPIA markedly reduced nicotine-elicited habituated locomotion. CntxMII effects on nicotine self administration are under investigation.

Conclusions: 

Present data demonstrate that midbrain alpha6beta2* nAChRs are necessary for two main effects of systemic nicotine, i.e., DA release in nAc and habituated locomotion, and suggest that they may be essential to mediate nicotine addictive properties.