The dopamine innervation of the visceral cortex mediates the aversive effects of opiates.

We have previously reported that opiates acting on peripheral receptors produce aversive effects whereas opiates acting on central brain receptors produce rewarding effects. The neurotransmitter dopamine (DA) has previously been implicated in both opiate reinforcing (positive) and aversive (negative) effects. We, therefore, chose to investigate the effects of disruption of DA systems on these two motivational properties of the opiate, morphine. Moreover, we sought to determine the brain site where dopamine might act as a mediator of these motivational effects. One group of rats received 6-hydroxydopamine (6-OHDA) lesions of the visceral (agranular insular) cortex to destroy dopaminergic innervation to this area. A separate group of animals were pretreated with intraperitoneal (IP) injections of the DA receptor blocker, alpha-flupenthixol (0.8 mg/kg), followed in both groups by 15 mg/kg (IP) morphine. Both 6-OHDA-lesioned and alpha-flupenthixol-pretreated subjects failed to develop the normal aversion to saccharin seen in control groups following conditioned taste aversion training with morphine. In a place conditioning paradigm, the aversive effects produced by low IP injections of morphine (acting on peripheral receptors) were blocked by 6-OHDA lesions of the visceral cortex. However, DA depletion of the visceral cortex did not disrupt the ability of animals to acquire a morphine place preference. Taken together, these results indicate that DA innervation of the visceral cortex mediates the aversive, but not the rewarding, properties of opiates.