Life Sciences, Vol. 31, pp. 2339-2342 Pergamon Press Printed in the U.S.A. OPIOID PHARMACOLOGY IN THE RAT HIPPOCAMPAL SLICE Rita J. Valentino, Elizabeth Bostock, and Raymond Dingledine Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, N.C. 27514 (Received in final form June 14, 1982) Summary The ability of several opioids in potentiating the synoptic activation of CAI pyramidal cells in the rat hippocampal slice w~e compared. Morphine and the opioid peptides, (D-ala , D-leu~)-enkephalin (DADL) , morphiceptin, B-endorphin, and Tyr-D-Ser-Gly-Phe-Leu-Thr (DSThr) caused a concentration-dependent, naloxone-reversible shift to the left in the input-output (IO) curve constructed by plotting the population spike as a function of the field EPSP. These opioids then produced an increase in the size of the population spike while leaving the EPSP unaffected. In contrast, the kappa agonist prototype, ethylketazoeine, had no effect on the IO curve when perfused in concentrations up to 10 ~M. The rank order ~f potency for the opioids in the CAI region of the hippocampus was DADL>DSThr> ~-endorphin>morphiceptin> morphine>>ethylketazocine. Thus, opiolds that are more specific for delta opiate receptors were the most potent and mu receptor agonists, the least potent in this action. Taken together with previous studies suggesting that morphine and DADL may interact with a common opiate receptor in the CAI region, the results are consistent with the notion that these epileptiform effects may be primarily mediated by delta opiate receptors in this area although the potency of morphiceptin indicates that mu receptors play some role in this effect. The existence of multiple opiate receptors has been supported by behavioral, physiological, and biochemical evidence (for review, see I). In addition, it has been proposed that the different receptor subtypes mediate the different pharmacological effects of opioids. For example, the receptor subtype for which morphine shows specificity (mu) has been postulated to mediate opioid analgesia while the delta receptor subtype for which enkephalins show a greater specificity are thought to play a primary role in limbic seizure activity (2,3). Thus, it has become important to determine the predominant opiate receptor subtype involved in specific physiological changes produced by these drugs. This has been done in peripheral tissues such as the guinea pig ileum and mouse vas deferens by determining the order of potency of several opioid agonists, sensitivity to antagonism by naloxone, and cross desensitization studies. In the present study, we determined the order of potency for various opioids in facilitating synoptic transmission in the CAI region of the hippocampus. I. This study was supported by NIH grants DA 02360 and NS-07166, a NIDA postdoctoral fellowship to R.J V. and a Sloan Research Fellowship to R.D. 2. Present address: The Salk Institute, P.O. Box 85800, San Diego, CA 92138. 0024-3205/82/202339-04503.00/0 Copyright (c) 1982 Pergamon Press Ltd.