Effects of apomorphine on morphine analgesia during the state of dopaminergic supersensitivity after chronic treatment with haloperidol

Morphine induced-reduction in response to a repetitive electrical stimulation of the tail was measured in acute rats and rats chronically treated with haloperidol (1 mg/kg/d, for 7 d) following pretreatment with apomorphine. In acute experiments, a significant enhancement of the anti-struggling action of morphine was produced by haloperidol (1 mg/kg, i.p.). Low doses of apomorphine (30-480 micrograms/kg, i.p.) had no influence on the suppressing action of morphine on the struggling response induced by the tail stimulation. Following chronic treatment with haloperidol, the inhibitory action of morphine on the tail stimulation-induced struggling response was dose-dependently inhibited by very low doses of apomorphine (60-480 micrograms/kg, i.p.). A significant increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels was observed after administration of haloperidol or morphine in acute rats, whereas no change in DOPAC levels was found after administration of morphine or apomorphine in chronically haloperidol-treated rats. In these animals, basal striatal DOPAC levels were significantly decreased compared with those of vehicle-treated animals controls. The present results suggest that in rats treated chronically with haloperidol, the suppressive action of a low dose of apomorphine on morphine analgesia is due to an increased sensitivity of postsynaptic dopaminergic receptors to apomorphine.