Opioid receptor regulation of 5-hydroxytryptamine release from the rat hippocampus measured by in vivo microdialysis

Abstract

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 solution (2 [mu]l/min), and extracellular levels of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were estimated by assaying their concentration in the dialysate by HPLC-ECD. Addition of potassium (K+, 60 and 120 mM) to the perfusate evoked a concentration-dependent release of 5-HT, but did not alter extracellular 5-HIAA levels. Co-perfusion of morphine (0.1 to 10 [mu]M) with K+ (120 mM) produced a concentration-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 [mu]M)-induced inhibition of 5-HT release. Naltrexone alone did not alter significantly either extracellular 5-HT levels or the release of 5-HT evoked by K+. Neither co-perfusion with [-Pen2, -Pen5]-enkephalin (DPDPE, 1 to 10 [mu]M), an agonist selective for [delta]-opioid receptors, nor with U-69593 (10 [mu]M), an agonist selective for [kappa]-opioid receptors, modified the K+ (120 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.