Figure 1. Dopamine receptor blockade or lesions of the mesolimbic dopamine system decrease cocaine reward but not heroin reward.

a | The effect of dopamine receptor blockade: rats were trained to lever press for intravenous heroin (0.06 mg kg⁻¹ per infusion) or cocaine (0.75 mg kg¹ per infusion) on a fixed-ratio 1 (FR1) reinforcement schedule (each lever press was reinforced with drug infusion). After stable self-administration, the rats were injected on different days with different doses of the dopamine receptor antagonist a-flupenthixol (left part). Lower doses (0.1 or 0.2 mg kg⁻¹) of a-flupenthixol increased cocaine intake but not heroin intake (right part); this effect presumably reflects a compensatory response to offset a decrease in the rewarding effects of cocaine but not heroin. A higher dose of a-flupenthixol (0.4 mg kg⁻¹), which causes sedation, decreased both heroin and cocaine self-administration (right part). b | The effect of dopaminergic lesions: rats were trained to self-administer heroin or cocaine, as above. After stable self-administration, dopamine terminals in the nucleus accumbens (NAc) were lesioned with 6-hydroxydopamine (6-OHDA) (left part). Post-lesion responding for cocaine decreased over days, reflecting extinction of cocaine-reinforced responding. By contrast, post-lesion responding for heroin increased over days, reflecting recovery of the rewarding effects of heroin (right part). DA, dopamine; DAR, dopamine receptor; DAT, dopamine transporter; GABAR, GABA recptor; MOR, mu opioid receptor; VTA, ventral tegmental area. Part a is modified, with permission, from REF. 20 © (1982) Springer. Part b is modified, with permission, from REF 21 © (1984) Springer.