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The distinction is critical, as drug self-administration (SA) can induce neurotransmission and cellular excitability changes that passive drug administration does not. In this study, we probed the question of whether medial habenula (MHb) nAChRs are functionally augmented by nicotine SA. Male rats were implanted with an indwelling jugular catheter and trained to nose poke for nicotine infusions. A saline SA group controlled for non-specific responding and nicotine-associated visual cues. Using patch-clamp whole-cell recordings and local application of acetylcholine, we observed robust functional enhancement of nAChRs in MHb neurons from rats with a history of nicotine SA. To determine whether upregulated receptors are generally enhanced or directed to specific cellular compartments, we imaged neurons during recordings using two-photon laser scanning microscopy (2PLSM). nAChR activity at the cell soma and on proximal and distal dendrites was examined by local nicotine uncaging using a photoactivatable nicotine (PA-Nic) probe and focal laser flash photolysis. Results from this experiment revealed strong nAChR enhancement at all examined cellular locations. Our study demonstrates nAChR functional enhancement by nicotine SA, confirming that volitional nicotine intake sensitizes cholinergic systems in the brain. This may be a critical plasticity change supporting nicotine addiction.<\/jats:p>","DOI":"10.1523\/eneuro.0197-20.2020","type":"journal-article","created":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T17:47:43Z","timestamp":1594921663000},"page":"ENEURO.0197-20.2020","source":"Crossref","is-referenced-by-count":25,"title":["Nicotine Self-Administration Induces Plastic Changes to Nicotinic Receptors in Medial Habenula"],"prefix":"10.1523","volume":"7","author":[{"given":"Xiao-Tao","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenton R.","family":"Tucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8141-8577","authenticated-orcid":false,"given":"Ryan M.","family":"Drenan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2020,7,16]]},"reference":[{"key":"2023041302145660000_7.4.ENEURO.0197-20.2020.1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23167"},{"key":"2023041302145660000_7.4.ENEURO.0197-20.2020.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2816-18.2019"},{"key":"2023041302145660000_7.4.ENEURO.0197-20.2020.3","doi-asserted-by":"crossref","unstructured":"Arvin MC , Wokosin DL , Banala S , Lavis LD , Drenan RM (2019b) Probing nicotinic acetylcholine receptor function in mouse brain slices via laser flash photolysis of photoactivatable nicotine. 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