Protein degradation by the UPS in the NAcc is involved in intra-VTA morphine self-administration. Mice received intra-NAcc injections of lactacystin or DMSO before each session of intra-VTA morphine or highly palatable food (crisps) self-administration in the Y-maze. (a) Representative microphotographic view of injection sites in animals treated with DMSO (left) and lactacystin (right). (b) Schematic localization of injection sites of DMSO (squares) and lactacystin (circles) in coronal sections ranging from +1.7 to +0.86 mm from Bregma. (c) Mice were exposed to intra-VTA morphine or aCSF self-administration. DMSO-treated animals (open circles, n=6) increased gradually their number of choice of the rewarded arm, whereas lactacystin animals did not (full circles, n=9). No preference was observed for the control group receiving aCSF into the VTA (squares, DMSO: n=6 and lactacystin: n=8). (d) Mice receiving either lactacystin (n=6) or DMSO (n=6) infusions into the NAcc developed a preference for the highly palatable food-rewarded arm. Data are presented as mean number of entries in the rewarded arm over 10 successive trails±SEM for each daily session.*p<0.05, **p<0.01, ***p<0.001 for morphine vs aCSF or crisps vs chance (5 over 10 trials). $p<0.05 for lactacystin vs vehicle (DMSO).