{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:43:53Z","timestamp":1789062233288,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2020,8,30]],"date-time":"2020-08-30T00:00:00Z","timestamp":1598745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Amphetamine (AMPH) use disorder is a serious health concern, but, surprisingly, little is known about the vulnerability to the moderate and compulsive use of this psychostimulant and its underlying mechanisms. Previous research showed that inherited serotonin transporter (SERT) down\u2010regulation increases the motor response to cocaine, as well as moderate (as measured during daily 1\u2010h self\u2010administration sessions) and compulsive (as measured during daily 6\u2010h self\u2010administration sessions) intake of this psychostimulant. Here, we sought to investigate whether these findings generalize to AMPH and the underlying mechanisms in the nucleus accumbens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>In serotonin transporter knockout (SERT<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type control (SERT<jats:sup>+\/+<\/jats:sup>) rats, we assessed the locomotor response to acute AMPH and i.v. AMPH self\u2010administration under short access (ShA: 1\u2010h daily sessions) and long access (LgA: 6\u2010h daily sessions) conditions. Twenty\u2010four hours after AMPH self\u2010administration, we analysed the expression of glutamate system components in the nucleus accumbens shell and core.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>We found that SERT<jats:sup>\u2212\/\u2212<\/jats:sup> animals displayed an increased AMPH\u2010induced locomotor response and increased AMPH self\u2010administration under LgA but not ShA conditions. Further, we observed changes in the vesicular and glial glutamate transporters, NMDA and AMPA receptor subunits, and their respective postsynaptic scaffolding proteins as function of SERT genotype and AMPH exposure (baseline, ShA, and LgA), specifically in the nucleus accumbens shell.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>We demonstrate that SERT gene deletion increases the psychomotor and reinforcing effects of AMPH and that the latter is potentially mediated, at least in part, by homeostatic changes in the glutamatergic synapse of the nucleus accumbens shell and\/or core.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15211","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T18:05:29Z","timestamp":1595959529000},"page":"4532-4547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Hypersensitivity to amphetamine's psychomotor and reinforcing effects in serotonin transporter knockout rats: Glutamate in the nucleus accumbens"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8045-3146","authenticated-orcid":false,"given":"Lucia","family":"Caffino","sequence":"first","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences Universit\u00e0 degli Studi di Milano  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel M. 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