OPIOID EFFECTS ON SPINAL [H-3] 5-HYDROXYTRYPTAMINE RELEASE ARE NOT RELATED TO THEIR ANTINOCICEPTIVE ACTION

Several opioid compounds were evaluated for an ability to modulate the K+-stimulated release of [H-3]serotonin ([H-3]5-hydroxytryptamine, [H-3]5-HT) from rat spinal cord synaptosomal and tissue slice preparations. Selective kappa-opioid receptor agonists depressed K+-stimulated release of the radiolabelled transmitter from both tissue preparations, an effect which was reversed by norbinaltorphimine. Conversely, the selective mu- and delta-opioid receptor agonists [D-Ala(2),NMePhe(4),Gly-ol(5)]enkephalin (DAMGO) and [D-Pen(2),D-Pen(5)]enkephalin (DPDPE), respectively, enhanced the Kc-stimulated release of [H-3]5-HT. This effect was only seen using the tissue slice preparation. When used at concentrations near its reported K-d for mu-opioid receptors, the selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) blocked the action of DAMGO, but had no effect on the action of DPDPE. However, higher concentrations of CTOP, as well as all effective concentrations of selective delta-opioid receptor antagonists, blocked the action of both DAMGO and DPDPE. All agonist effects on spinal 5-HT release, regardless of the tissue preparation, were only seen at high (mu M) concentrations. Moreover, effects of the opioid agonists were not consistent with the reported involvement of spinal 5-HT neurotransmission in the mediation of their antinociceptive action. Thus, the ability of opioids to modulate spinal 5-HT release appears to be of minimal physiological significance.