Morphine and methadone-induced antinociception in rats permanently depleted of brain dopamine.

The purpose of the present study was to evaluate the role of brain norepinephrine (NE) and/or dopamine (DA) in the production of the antinociceptive effects of morphine and methadone. Rats were permanently depleted of brain NE and/or DA via 6-hydroxydopamine (6-OHDA) treatments at two weeks of age. Six to eight weeks later, the antinociceptive activity of morphine and methadone was determined in control, NE and DA-depleted, and DA-depleted rats by tail-flick methods. Both dose-response and time-duration studies were conducted. The data obtained suggested that DA was important to morphine, but not to methadone-induced antinociception. However, this relationship appeared contingent upon the level of DA-depletion. An antagonism of morphine's effects was observed when DA levels were down by at least 85% whereas a facilitation of morphine's effect occurred when DA levels were 50% or less. These findings were discussed in relation to more recent concepts suggesting that: 1) DA-related behaviors are contingent upon a balance between excitatory and inhibitory DA neuron pools, and 2) antinociception may (in relation to DA) also be controlled via a balance between this system (DA) and NE systems. Thus, it was suggested that the potency of morphine's antinociceptive effects appears contingent upon a balance between one or more of these neuron pathways.