Binding of [3H]spiroperidol to striatal membranes of rats treated chronically with morphine. Influence of Pro-Leu-Gly-NH2 and cyclo(Leu-Gly).

The effect of the chronic administration of morphine to Sprague-Dawley rats on striatal dopamine receptors labelled with [3H]spiroperidol was determined. For chronic administration of morphine, rats were implanted subcutaneously with four morphine pellets (each containing 75 mg of morphine free base) during a 3-day period. Placebo pellet-implanted rats served as controls. Twenty-four hours after the removal of the pellet binding of [3H]spiroperidol to striatal dopamine receptors was determined. Rats receiving morphine showed no difference in the total number of binding sites (Bmax value) but there was a 60% decrease in the apparent dissociation constant (Kd value) compared with placebo controls. The effect of two peptides, Pro-Leu-Gly-NH2 and cyclo(Leu-Gly) (2 mg/kg), which have been shown to inhibit tolerance to and dependence on morphine, on the changes in the binding of [3H]spiroperidol induced by the implantation of morphine pellets was also determined. Both peptides antagonized the decreases in Kd values induced by the administration of morphine. However, when administered chronically by themselves, the peptides had no effect on either the Bmax or Kd values of [3H]spiroperidol. It is concluded that the behavioral supersensitivity of dopamine receptors and the genesis of tolerance-dependence to opiates may be related to the affinity and not to the density of striatal dopamine receptors.