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These relationships are recapitulated in preclinical models, where rats that exhibit increased exploratory activity in novel environments (high responders\u2014HR) acquire self\u2010administration of psychostimulants more rapidly compared to rats that display low novelty exploration (low responders\u2014LR). Dopamine release dynamics in the nucleus accumbens (NAc) covaries with response to novelty, and differences in dopaminergic signalling are thought to be a major underlying driver of the link between novelty seeking and drug use vulnerability. Accumbal dopamine release is controlled by local microcircuits including modulation through glutamatergic and nicotinic acetylcholine receptor (nAChR) systems, but whether these mechanisms contribute to disparate dopamine signalling across novelty phenotypes is unclear. Here, we used ex vivo voltammetry in the NAc of rats to determine if \u03b17 nAChRs contribute to differential dopamine dynamics associated with individual differences in novelty exploration. We found that blockade of \u03b17 nAChRs attenuates tonic dopamine release evoked by low\u2010frequency stimulations across phenotypes but that phasic release is decreased in LRs while HRs are unaffected. These stimulation frequency\u2010 and phenotype\u2010dependent effects result in a decreased dynamic range of release exclusively in LRs. Furthermore, we found that differential \u03b17 modulation of dopamine release in LRs is dependent on AMPA but not NMDA receptors. These results help to form an understanding of the local NAc microcircuitry and provide a potential mechanism for covariance of dopamine dynamics and sensitivity to the reinforcing effects of drugs of abuse.<\/jats:p>","DOI":"10.1111\/ejn.15620","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T02:33:17Z","timestamp":1644460397000},"page":"1162-1173","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["\u03b17 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3683-8633","authenticated-orcid":false,"given":"Amy C.","family":"Leach","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth G.","family":"Pitts","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cody A.","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Center for Addiction Research Vanderbilt University  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-7955","authenticated-orcid":false,"given":"Mark J.","family":"Ferris","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Wake Forest School of Medicine  Winston\u2010Salem North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.188"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158136"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0578-x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.05.009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300536"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.05.011"},{"issue":"468","key":"e_1_2_10_8_1","first-page":"1","article-title":"Making choice between competing rewards in uncertain vs. safe social environment: Role of neuronal nicotinic receptors of acetylcholine","volume":"7","author":"Chabout J.","year":"2013","journal-title":"Frontiers in Human Neuroscience"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.10.047"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e32832f0176"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099020"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(92)90249-2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.06.015"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301617"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2017-06.2007"},{"issue":"173","key":"e_1_2_10_16_1","first-page":"1","article-title":"Phasic dopamine release magnitude tracks individual differences in sensitization of locomotor response following a history of nicotine exposure","volume":"10","author":"Fennell A. 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