enkephalin--ala(2)-mephe(4)-gly(5)- and 5-carboxamidotryptamine

The changes in the latency for tail withdrawal in response to noxious heating of the skin induced by microinjection of opioid or serotonergic agonists into the anterior pretectal nucleus (APtN) was studied in rats. The mu-opioid agonist DAMGO (78 and 156 picomol), but not the delta-opioid agonist DADLE (70 and 140 pmol), the kappa-opioid agonist bremazocine (0.24 and 0.48 nanomol) or the sigma-opioid agonist N-allylnormetazocine (0.54 nanomol), produced a dose-dependent antinociceptive effect. The 5-HT1 agonist 5-carboxamidotryptamine (19 and 38 nanomol) and the 5-HT1B agonist, CGS 12066B (1.12 and 2.24 nanomol), but not the non-selective 5-HT agonist m-CPP (41 to 164 nanomol), 5-HT2 agonist alpha-methylserotonin (36 and 72 nanomol) and 5-HT3 agonist 2-methylserotonin (36 and 72 nanomol), produced a dose-dependent antinociceptive effect. These results indicate that the antinociceptive effects of opioid or serotonergic agonists microinjected into the APtN depend on drug interaction with local mu or 5-HT1B receptors, respectively.

Topics: Analgesics; Animals; Benzomorphans; Brain; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Microinjections; Pain; Phenazocine; Piperazines; Quinoxalines; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Serotonin; Serotonin Receptor Agonists

Nucleus raphe magnus contains a large population of raphe-spinal serotonergic neurons that are thought to be involved in descending control of pain transmission and the modulation of opioid analgesia. Intracellular recordings were made from nucleus raphe magnus neurons in the slice preparation. Cells were divided into two groups, primary and secondary cells, based on the action potential waveform and response to opioids, as reported previously. In some experiments, cells were filled with biocytin and 5-hydroxytryptamine-containing cells were identified immunohistochemically. Of the primary cells that were filled with biocytin, 93% stained for 5-hydroxytryptamine; 90% of biocytin-filled secondary cells were unlabeled for 5-hydroxytryptamine. Previous studies have shown that primary cells are disinhibited by opioids; the finding that most primary cells are serotonergic suggests that at least some 5-hydroxytryptamine-containing neurons in the nucleus raphe magnus are excited by opioid analgesics. 5-Hydroxytryptamine hyperpolarized cells in both primary and secondary cell groups. The 5-hydroxytryptamine agonists (+/-)-2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide and 5-carboxamidotryptamine mimicked this action of 5-hydroxytryptamine, indicating that the 5-hydroxytryptamine 1A-subtype mediated this hyperpolarization. The hyperpolarization was mediated by an increase in potassium conductance that rectified inwardly. Local electrical stimulation of afferents evoked an inhibitory postsynaptic potential in primary cells. The inhibitory postsynaptic potential reversed polarity at the potassium equilibrium potential and was blocked by 5-hydroxytryptamine 1A receptor antagonists. It is proposed that the 5-hydroxytrypamine1A receptor on serotonergic primary cells may function as an autoreceptor to regulate the activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Electric Stimulation; Electrophysiology; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Evoked Potentials; In Vitro Techniques; Indoles; Membrane Potentials; Neurons; Quinoxalines; Raphe Nuclei; Rats; Rats, Wistar; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Tropisetron