OPIOID RECEPTOR REGULATION OF 5-HYDROXYTRYPTAMINE RELEASE FROM THE RAT HIPPOCAMPUS MEASURED BY INVIVO MICRODIALYSIS

The modulation of serotonin (5-HT) release by opioid receptors in the hippocampus of the awake, unrestrained rat was evaluated by use of in vivo microdialysis. The hippocampus was perfused with Ringer's solutio n (2 mul/min), and extracellular levels of 5-HT and its major metaboli te, 5-hydroxyindoleacetic acid (5-HIAA) were estimated by assaying the ir concentration in the dialysate by HPLC-ECD. Addition of potassium ( K+, 60 and 120 mM) to the perfusate evoked a concentration-dependent r elease of 5-HT, but did not alter extracellular 5-HIAA levels. Co-perf usion of morphine (0.1 to 10 muM) with K+ (120 mM) produced a concentr ation-dependent reduction of 5-HT release. Naltrexone (0.03 to 3 mg/kg , i.p.), a relatively selective mu-opioid receptor antagonist, blocked in a dose-dependent manner the morphine (10 muM)-induced inhibition o f 5-HT release. Naltrexone alone did not alter significantly either ex tracellular 5-HT levels or the release of 5-HT evoked by K+. Neither c o-perfusion With [D-Pen2, D-Pen5]-enkephalin (DPDPE, 1 to 10 muM), an agonist selective for delta-opioid receptors, nor with U-69593 (10 muM ), an agonist selective for kappa-opioid receptors, modified the K+ (1 20 mM)-evoked release of 5-HT. These findings indicate that mu-opioid receptors modulate the physiological release of 5-HT from serotonergic neurons in the rat hippocampus.