| First Author | Ables JL | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 49 | Pages | 13012-13017 |
| PubMed ID | 29158387 | Mgi Jnum | J:254447 |
| Mgi Id | MGI:6103158 | Doi | 10.1073/pnas.1717506114 |
| Citation | Ables JL, et al. (2017) Retrograde inhibition by a specific subset of interpeduncular alpha5 nicotinic neurons regulates nicotine preference. Proc Natl Acad Sci U S A 114(49):13012-13017 |
| abstractText | Repeated exposure to drugs of abuse can produce adaptive changes that lead to the establishment of dependence. It has been shown that allelic variation in the alpha5 nicotinic acetylcholine receptor (nAChR) gene CHRNA5 is associated with higher risk of tobacco dependence. In the brain, alpha5-containing nAChRs are expressed at very high levels in the interpeduncular nucleus (IPN). Here we identified two nonoverlapping alpha5 (+) cell populations (alpha5- (Amigo1) and alpha5- (Epyc) ) in mouse IPN that respond differentially to nicotine. Chronic nicotine treatment altered the translational profile of more than 1,000 genes in alpha5- (Amigo1) neurons, including neuronal nitric oxide synthase (Nos1) and somatostatin (Sst). In contrast, expression of few genes was altered in the alpha5- (Epyc) population. We show that both nitric oxide and SST suppress optically evoked neurotransmitter release from the terminals of habenular (Hb) neurons in IPN. Moreover, in vivo silencing of neurotransmitter release from the alpha5- (Amigo1) but not from the alpha5- (Epyc) population eliminates nicotine reward, measured using place preference. This loss of nicotine reward was mimicked by shRNA-mediated knockdown of Nos1 in the IPN. These findings reveal a proaddiction adaptive response to chronic nicotine in which nitric oxide and SST are released by a specific alpha5(+) neuronal population to provide retrograde inhibition of the Hb-IPN circuit and thereby enhance the motivational properties of nicotine. |
