DIFFERENCES IN THE BINDING OF [H-3] [D-SER2,THR6]LEUCINE-ENKEPHALIN AND [H-3] [D-PEN2,D-PEN5]ENKEPHALIN TO BRAIN MEMBRANES OF MORPHINE TOLERANT-DEPENDENT RATS

The effect of morphine tolerance-dependence and abstinence on the characteristics of delta-opiate receptors was determined in male Sprague-Dawley rats. Two ligands used for characterizing the receptors were [H-3][D-Ser2,Thr6]leucine-enkephalin (H-3]DSTLE) and [H-3][D-Pen2,D-Pen5]enkephalin ([H-3]DPDPE). Rats were implanted s.c. under light ether anesthesia with six morphine pellets (each containing 75 mg of morphine free base). Rats which served as controls were implanted similarly with placebo pellets. Two sets of rats were used. In one group of rats, the pellets were left intact (tolerant-dependent) at the time of sacrificing and in the other the pellets had been removed 18 h earlier (abstinent). The spinal cord and brain regions (amygdala, hippocampus, hypothalamus, corpus striatum, mid-brain, pons and medulla and cortex) were dissected for binding studies. The binding of [H-3]DSTLE to membranes of cerebral cortex of morphine-tolerant-dependent rats was decreased in comparison to control rats, and was due to a decrease in B(max) rather than K(d) value. The binding of [H-3]DSTLE to other brain regions or spinal cord of morphine-tolerant-dependent and abstinent rats did not differ from their respective controls. On the other hand, the binding of [H-3]DPDPE was unaffected in any brain region or the spinal cord of morphine-tolerant-dependent and abstinent rats when compared to their controls. The decrease in binding of [H-3]DSTLE to cortical membranes of morphine-tolerant-dependent rats amounted to 15%. Since DSTLE also binds to mu-opiate receptors, which have earlier been shown to be decreased in cortex of morphine-tolerant-dependent rats, and the binding of a more selective delta-opiate ligand [H-3]DPDPE was unaffected, it is concluded that central delta-opiate receptors do not play a role in the development of morphine-induced tolerance-dependence or abstinence processes in the rat.