{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:31:07Z","timestamp":1792143067413,"version":"4.4.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> The rewarding effects of drugs of abuse are associated with the dopaminergic system in the limbic circuitry. Nicotine exposure during adolescence is linked to increased use of drugs of abuse with nicotine and methamphetamine (METH) commonly used together. Nicotine acts on neuronal nicotinic acetylcholine receptor (nAChR) systems, critical for reward processing and drug reinforcement, while METH leads to a higher dopamine (DA) efflux in brain reward regions. A human single nucleotide polymorphism (SNP) in the 3\u2032-untranslated region (UTR) of the \u03b16 nicotinic receptor subunit gene (<jats:italic>CHRNA<\/jats:italic>6, rs2304297), has been linked with tobacco\/nicotine and general substance use during adolescence. Using CRISPR-Cas9 genomic engineering, our lab recapitulated the <jats:italic>CHRNA<\/jats:italic>6 3\u2032UTR<jats:sup>C123G<\/jats:sup> SNP, generating \u03b16<jats:sup>CC<\/jats:sup> and \u03b16<jats:sup>GG<\/jats:sup> allele carriers in Sprague Dawley rats. We hypothesized the <jats:italic>CHRNA<\/jats:italic>6 3\u2032UTR<jats:sup>C123G<\/jats:sup> SNP would sex- and genotype-dependently enhance nicotine-induced METH self-administration as well as nicotine-induced DA overflow in the nucleus accumbens shell of adolescent \u03b16<jats:sup>GG<\/jats:sup> and \u03b16<jats:sup>CC<\/jats:sup> carriers.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Adolescent male and female rats underwent a 4-day sub-chronic, low-dose (0.03\u00a0mg\/kg\/0.1\u00a0mL, x2) nicotine pretreatment paradigm to assess intravenous METH (0.02\u00a0mg\/kg\/0.1\u00a0mL) self-administration as well as nicotine- and METH (0.02\u00a0mg\/kg\/0.1\u00a0mL)-induced DA overflow in the nucleus accumbens shell (NAcS) using <jats:italic>in vivo<\/jats:italic> microdialysis coupled with high-performance liquid-chromatography-electrochemical detection (HPLC-ECD).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Nicotine pretreatment sex- and genotype-dependently enhanced subsequent METH self-administration in adolescent <jats:italic>CHRNA<\/jats:italic>6 3\u2032UTR<jats:sup>C123G<\/jats:sup> SNP rats. Further nicotine and METH-induced DA overflow is observed in \u03b16<jats:sup>CC<\/jats:sup> females as compared to \u03b16<jats:sup>GG<\/jats:sup> females, with METH-induced DA overflow enhanced in \u03b16<jats:sup>GG<\/jats:sup> males when compared to \u03b16<jats:sup>CC<\/jats:sup> males.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> These findings demonstrate that the <jats:italic>CHRNA<\/jats:italic>6 3\u2032-UTR<jats:sup>C123G<\/jats:sup> SNP can sex- and genotype-dependently impact adolescent nicotine-induced effects on METH self-administration and stimulant-induced DA overflow in reward regions of the brain.<\/jats:p>","DOI":"10.3389\/fphar.2024.1445303","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T05:03:23Z","timestamp":1723611803000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Sub-chronic nicotine exposure influences methamphetamine self-administration and dopamine overflow in a sex-and genotype-dependent manner in humanized CHRNA6 3\u2032-UTR SNP (rs2304297) adolescent rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Diana","family":"Carre\u00f1o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Facundo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjelica","family":"Cardenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrdad","family":"Lotfipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1152\/physrev.00015.2008","article-title":"Mammalian nicotinic acetylcholine receptors: from structure to function","volume":"89","author":"Albuquerque","year":"2009","journal-title":"Physiol. 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