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Abstract
Morphine produces robust increases in locomotor activity in mice. Recent data indicate
that dopamine (DA) D2/3 agonists attenuate the discriminative stimulus and antinociceptive
effects of mu opioid agonists such as morphine. The present study was designed to
determine the extent to which D2/3 receptor activation and blockade can modulate morphine-induced
locomotion using a novel cumulative dosing procedure in Swiss-Webster mice. The results
indicate that morphine-induced locomotion is nonsignificantly attenuated by the D2/3
agonists quinelorane and quinpirole, whereas the D2/3 antagonists eticlopride and
nafadotride, as well as the partial D2/3 agonist BP897, significantly reduced morphine-induced
locomotion. To determine the specificity of this modulation, these agonists and antagonists
were examined in combination with caffeine, a drug that also indirectly alters DAergic
activity. Unlike the effects on morphine, caffeine-induced locomotion was unaltered
by eticlopride, nafadotride and BP897, but was attenuated by quinelorane and quinpirole.
These results indicate that modulation of D2/3 receptors can, in turn, alter the locomotor-activating
effects of morphine.