Effects of 6-hydroxydopamine-induced depletions of brain catecholamines or dopamine on meperidine antinociception in rats.

The participation of brain norepinephrine (NE) and dopamine (DA) in the production of the antinociceptive effect of meperidine was investigated. Rats were permanently depleted of brain catecholamines via 6-hydroxydopamine treatments at 2 weeks of age. 6-8 weeks later, the antinociceptive activity of meperidine was determined in control, NE- and DA-depleted, and DA-depleted rats by both the tail-flick and hot-plate methods. The antinociceptive activity of meperidine was reduced in DA-depleted male rats. In DA-depleted female rats, however, the antinociceptive activity was increased at low doses of meperidine and decreased only at higher doses of the drug. In male NE + DA-depelted rats, the activity was generally intermediate between that seen in DA-depleted and control rats. No consistent change in the activity of meperidine was observed in female NE + DA-depleted rats.