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The incretin hormones glucose\u2010dependent insulinotropic polypeptide (GIP) and glucagon\u2010like peptide\u20101 (GLP\u20101) have emerged as novel treatment targets, as they appear to influence both reward\u2010related behaviours associated with addictive substances and body weight regulation. Whether recently developed multi\u2010receptor incretin agonists such as tirzepatide, a long\u2010acting dual GIP\/GLP\u20101 receptor agonist, affect nicotine\u2010induced behaviours remains unstudied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We investigated whether tirzepatide affects nicotine\u2010induced behaviours (locomotor stimulation and expression of locomotor sensitisation, expression and reinstatement of conditioned place preference) and related neurochemistry (in vivo microdialysis and ex vivo tissue neurochemical analysis) in male mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Tirzepatide attenuated nicotine\u2010induced locomotor stimulation in a dose\u2010related manner, and reduced nicotine\u2010induced place preference, and in vivo accumbal dopamine release. Furthermore, tirzepatide suppressed reinstatement of nicotine place preference and prevented the expression of locomotor sensitisation, indicating effects beyond acute reward processing. Ex vivo neurochemical analysis of addiction\u2010related brain regions in nicotine\u2010sensitised mice revealed that tirzepatide blocked nicotine\u2010induced dopamine elevations in the nucleus accumbens, ventral tegmental area and lateral septum. Furthermore, tirzepatide restored levels of multiple neurotransmitter systems, such as GABA, in a brain region\u2010specific manner, suggesting possible effects beyond dopaminergic signalling alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Collectively, these findings indicate that tirzepatide attenuates nicotine\u2010induced locomotor stimulation and dopamine release, as well as the expression and reinstatement of place preference, and the expression of locomotor sensitisation, in mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70678","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:21:07Z","timestamp":1790641267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The dual incretin agonist tirzepatide blunts 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