D1 receptor hypersensitivity in mice with low striatal D2 receptors facilitates select cocaine behaviors

Cross-sensitization between cocaine and a D1-like agonist suggests a common mechanism. a Experimental timeline. Mice were treated with saline- (gray) or SKF-81297 (blue) for 5 days and all mice were challenged with a cocaine injection 14 days later. b Horizontal locomotor activity during habituation (h), two saline sessions (s1, s2) and during 5 daily sessions of treatment with saline (black) or SKF-81297 (blue). Posthoc t-test: Saline vs. SKF-81297: *p？<？0.05. c Horizontal locomotor activity on cocaine challenge day before and after cocaine injection (red box) for mice pretreated with saline (black) or SKF-81297 (blue). d Normalized total counts during 1-h post cocaine challenge injection as a function of pre-challenge baseline for each mouse. Unpaired t-test, *p？<？0.05. e Experimental timeline. Cocaine-naive (left) or cocaine-pretreated (right, red box) mice received escalating SKF-81297 doses (blue box). f Horizontal locomotor activity before and after saline (black) or SKF 81297 (blue, 5？mg/kg) administration for mice with no previous cocaine experience (cocaine naive, left plot) or mice pretreated with cocaine that did not show cocaine sensitization (middle plot) and those that did show cocaine locomotor sensitization (right plot, “sensitized”). g Locomotor activity to all doses of SKF-81297 tested for each group: cocaine na？ve (black), cocaine-treated “non-sensitized” (red open), and cocaine-treated “sensitized” mice (red filled). Data is normalized to same-day, pre-injection baseline. Posthoc t-tests: * p？<？0.0