Opioid receptor regulation of 5-hydroxytryptamine release from the rat hippocampus measured by in vivo 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 solution (2 microliters/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 microM) 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 microM)-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 [D-Pen2, D-Pen5]-enkephalin (DPDPE, 1 to 10 microM), an agonist selective for delta-opioid receptors, nor with U-69593 (10 microM), 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.
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
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Yoshioka
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Matsumoto
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Togashi
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Smith
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Saito
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides; D003956:Dialysis; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008846:Micromanipulation; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D011957:Receptors, Opioid; D012701:Serotonin; D009271:Naltrexone; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C045444:U 69593; D011188:Potassium