Morphine differentially affects ventral tegmental and substantia nigra brain reward thresholds

In order to differentiate the roles of the nigrostriatal and mesolimbic-mesocortical dopamine systems in the action of opiates on dopaminergically mediated intracranial self-stimulation (ICSS), the effects of chronic morphine administration and acute naloxone administration on ICSS were tested in rats with electrode placements in the substantia nigra pars compacta (A-9) and the ventral tegmentum (A-10). Acute morphine (5.0 mg/kg SC) did not affect ICSS thresholds of rats with electrodes in the A-9 nucleus when tested 1, 3, 5, and 23 hours after administration. With repeated daily administration, though, these animals showed increases in thresholds which grew progressively larger with each day of morphine treatment. This threshold elevation was not reversed by naloxone given 0.5 hour after the final morphine treatment on the fifth day. In contrast, acute morphine significantly lowered self-stimulation thresholds in rats with A-10 placements. Tolerance to this facilitatory effect was evident with chronic administration. Naloxone attentuated the lowering of threshold caused by opiate administration in these A-10 animals. The present data suggest a specificity of action of opiates on different brain systems subserving reward and reinforcement. These findings also suggest that the mesolimbic-mesocortical system may play an important role in mediating the rewarding properties of morphine.