Glucagon like peptide (GLP-1) receptor agonists (GLP-1 RAs), such as Semaglutide, suppress food intake and are FDA approved to treat obesity. The primary mechanism of GLP-1 RAs involves interactions with the central nervous system, where GLP1 RA act in the hypothalamus or brainstem to reduce food intake. GLP-1 action on midbrain dopamine neurons in the VTA may also reduce food motivation and reward to suppress appetite. In addition to GLP1 RAs, new compounds with dual GLP1R and glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonism, such as tirzepatide, show greater weight loss in clinicals trial than GLP1 RAs only. In this study, we sought to examine how GLP1 RA (semaglutide) and GLP1/GIPR co-agonists (LY3298176 [Tirzepatide]), affect food motivation and dopamine release in the nucleus accumbens using in vivo GRAB-DA photometry. We measured dopamine release in the nucleus accumbens (mesolimbic pathway) in lean and obese C57BL/6 male and female mice in response to chow and high fat diet, as well as during operant conditioning to measure food motivation. Our findings revealed that mice treated with semaglutide, P19, and LY3298176 exhibit suppressed dopamine release and consumption of chow and palatable food, with the strongest suppression of dopamine release in lean mice. Notably, sex differences in dopamine release to were observed during both short- and long-term feeding experiments. In conclusion, GLP-1 RAs and GLP-1/GIP RCAs simultaneously suppress nucleus accumbens dopamine release and food intake in a sex-specific manner, highlighting effective obesity treatment may require suppression of food reward via the mesolimbic dopamine pathway.