DOPAMINE PLAYS A KEY ROLE IN REINFORCING VALUE OF OPIATES

Dopamine Plays a Key Role In Reinforcing Value Of Opiates



Dopamine Plays a Key Role In Reinforcing Value Of Opiates

While dopaminergic neurons project from the VTA to structures throughout the brain, the neurons heading to the NA have been repeatedly implicated in the rewarding properties of opioids. Systemic administration (into the body at large) of opiates increase dopamine turnover in the NA (Westerink et al, 1976), which suggests that opioids increase dopamine activity. It has been further demonstrated that opiates increase activity of early genes, c-fos, c-jun, and zif altering gene transcription (Graybiel et al., 1990), which suggests that opioids cause long-lasting and enduring changes in the cells of the NA.

Although dopamine excitation likely increases the rewarding effect of opioids, it appears that reinforcement is not contingent upon dopamine activation. A key study found that heroine self-administration continues after disruption of DA innervation in NA, which suggests that rewarding effects of opiates are only partially contingent on DA release in the NA (Koob and Bloom, 1988). The finding is consistent with the discovery that animals will self-administer opioids in the NA (Olds, 1982), which suggests that opioid activity in the NA has a rewarding effect independent of neurons from the VTA.

It is important to note that the animals will modify their behavior more to obtain opioids in the VTA (Olds, 1982), which suggests that the VTA activation produces a more rewarding effect than NA activation.

Another line of research suggests that dopaminergic input is not necessary for opioid reward. 6-OHDA lesions in NA, which specifically destroy dopaminergic neurons, did not affect lever press linked to opioid reward (Robbins et al., 1989).

Yet, it does appear that dopamine has an excitatory effect on opioid-induced reward. Dopamine antagonists slow response speed in reinforced tasks, but do not eliminate the response all together (Evenden and Robbins, 1983). A recent study also found potentiation of opioid activity by dopamine agonists, while dopamine antagonists inhibit opioid activity (Cook et al., 1999). On a cellular level, dopamine administration in NA tissue elicits changes in electrical activity when cell slices are placed in a test tube mimicking the brain's environment (Pennartz et al., 1992). In reviewing the body of research, dopamine seems to enhance the actions of opioids on reward in the NA, but does not appear to be required for reinforcement.

It is interesting to note that opioid and dopamine agonists alike, both substances associated with addiction, depress overall excitation in the NA (Pennartz et al., 1992). Yet, muscarinic agonists decrease excitation in the NA without altering addiction (Pennartz and Lopes da Silva, 1994).

NA involvement in opioid withdrawal and tolerance

The NA appears to be extremely sensitive to opioid withdrawal. Injecting an antagonist into a dependant animal can experimentally induce withdrawal. Low doses of the opiate antagonist, methylnaloxonium, disrupt operant performance when injected into NA of morphine-dependant rats (Stinus et al., 1990). Even though other structures were sensitive to withdrawal, the NA was by far the most sensitive (Stinus et ...