Binding of [ 3H]spiroperidol to striatal membranes of rats treated chronically with morphine : Influence of pro-Leu-Gly-NH 2 and cyclo(Leu-Gly)

Abstract

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 ( B max value) but there was a 60% decrease in the apparent dissociation constant ( K d value) compared with placebo controls. The effect of two peptides, Pro-Leu-Gly-NH 2 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 K d values induced by the administration of morphine. However, when administered chronically by themselves, the peptides had no effect on either the B max or K d 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.