Characterization of Opioid Receptors Modulating Noradrenaline Release in the Hippocampus of the Rabbit

It is concluded that NA release in the rabbit hippocampus is inhibited via K‐receptors; the results do not support the presence of modulatory μ‐ and δ‐ receptors in this tissue.

Abstract

Abstract: Noradrenaline (NA) release and its modulation via presynaptic opioid receptors were studied in rabbit hippocampal slices, which were preincubated with [ 3 H]NA, continuously superfused in the presence of 30 μ M cocaine and stimulated electrically. The evoked release of [ 3 H]NA was strongly reduced by the preferential K‐agonists ethylketocyclazocine, dynorphin A 1‐13 , dynorphin A, trans ‐3,4‐dichloro‐ N ‐methyl‐ N ‐[2‐(1‐pyrrolidinyl)‐cyclohexyl]‐benzeneacetamide (U‐50,488), and (–)‐5,9‐dimethyl‐2′‐OH‐2‐tetrahydrofurfuryl‐6,7‐benzomorphan [(–)‐MR 2034], whereas (+)‐MR 2035 [the (+)‐enantiomer of (–)‐MR 2034] was ineffective. In contrast, the preferential δ‐agonists Leu‐enkephalin, Met‐enkephalin, and D‐Ala 2 ,‐D‐Leu 5 ‐enkephalin (DADLE) as well as the μ‐agonists morphine, normorphine, D‐Ala 2 Gly‐ol 5 ‐enkephalin (DAGO), and β‐casomorphin 1‐4 amide (morphiceptin) were much less potent. However, in similar experiments on rat hippocampal slices DAGO (1 μ M ) was much more potent than ethylketocyclazocine (1 μ M ) or DADLE (1 μ M ). (–)‐ N ‐(3‐furylmethyl)‐α‐noretazocine [(–)‐MR 2266], 1 μ M , a preferential K‐antagonist, antagonized the effect of ethylketocyclazocine more potently than (–)‐naloxone or (+)‐MR 2267 [the (+)‐enantiomer of (–)‐MR 2266]. Given alone, (–)‐MR 2266 slightly and (+)‐MR 2267 (1 μ M each) greatly enhanced NA release, apparently due to α 2 ‐adrenoceptor blockade since their effects were completely abolished in the presence of yohimbine (0.1 μ M ). The effects of DADLE (1 μ M ) and DAGO (1 μ M ) were also antagonized by (–)MR 2266 (0.1 μ M ) but not by the δ‐antagonist N ,N‐diallyl‐Tyr‐Aib‐Phe‐Leu‐OH (ICI 174864), 0.3 μ M . It is concluded that NA release in the rabbit hippocampus is inhibited via K‐receptors; our results do not support the presence of modulatory μ‐ and δ‐receptors in this tissue. However, in the rat hippocampus μ‐receptors may modulate NA release.