| First Author | Peng C | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 7 | Pages | e0182142 |
| PubMed ID | 28759616 | Mgi Jnum | J:246834 |
| Mgi Id | MGI:5918336 | Doi | 10.1371/journal.pone.0182142 |
| Citation | Peng C, et al. (2017) Altered nicotine reward-associated behavior following alpha4 nAChR subunit deletion in ventral midbrain. PLoS One 12(7):e0182142 |
| abstractText | Nicotinic acetylcholine receptors containing alpha4 subunits (alpha4beta2* nAChRs) are critical for nicotinic cholinergic transmission and the addictive action of nicotine. To identify specific activities of these receptors in the adult mouse brain, we coupled targeted deletion of alpha4 nAChR subunits with behavioral and and electrophysiological measures of nicotine sensitivity. A viral-mediated Cre/lox approach allowed us to delete alpha4 from ventral midbrain (vMB) neurons. We used two behavioral assays commonly used to assess the motivational effects of drugs of abuse: home-cage oral self-administration, and place conditioning. Mice lacking alpha4 subunits in vMB consumed significantly more nicotine at the highest offered nicotine concentration (200 mug/mL) compared to control mice. Deletion of alpha4 subunits in vMB blocked nicotine-induced conditioned place preference (CPP) without affecting locomotor activity. Acetylcholine-evoked currents as well as nicotine-mediated increases in synaptic potentiation were reduced in mice lacking alpha4 in vMB. Immunostaining verified that alpha4 subunits were deleted from both dopamine and non-dopamine neurons in the ventral tegmental area (VTA). These results reveal that attenuation of alpha4* nAChR function in reward-related brain circuitry of adult animals may increase nicotine intake by enhancing the rewarding effects and/or reducing the aversive effects of nicotine. |
