ACUTE TOLERANCE TO THE EXCITATORY EFFECTS OF OPIOIDS IN THE RAT HIPPOCAMPUS

Prolonged iontophoretic administrations of delta- and mu-selective opi oid receptor agonists were conducted in the hippocampus of rats, in or der to study the possible development of acute tolerance to the excita tory effects of the opioids. Acute tolerance (AT) to the excitatory ef fects of the delta-selective opioid receptor agonist Tyr-D-Ser-Gly-Phe -Leu-Thr (DSLET) was observed when the drug was applied locally for 3- 5 min in the CA1 hippocampal pyramidal neurons, The acute tolerance wa s expressed as a decrease in the commissurally evoked spike responsive ness during peptide's administration and led to a long-lasting potenti ation of the population spike (PS) upon its withdrawal, In all cases, where AT and spike potentiation were evident, the population excitator y postsynaptic potential (pEPSP) remained unaltered. Pharmacological s tudies of AT and long-lasting spike potentiation showed the following: (1) the nonselective opioid receptor antagonist, naloxone, while effe ctive in blocking the excitatory effects of DSLET when applied prior a nd during the application of the latter, failed to exhibit any effect on the long-lasting potentiating effect of the opioid; and (2) during the spike potentiation phase, administration of DSLET exhibited a depr essant effect towards baseline values, This depressant effect of the o pioid was evident 2-3 min from the beginning of the application and wa s completely antagonized by naloxone. The above results show that the development of acute tolerance to the excitatory effects of the DSLET led to long-lasting spike potentiation, which manifests a withdrawal p henomenon. (C) 1995 Wiley-Liss, Inc.