Possible involvement of serotonergic neurotransmission in neurotensin but not morphine analgesia

Abstract

The purpose of this study is to determine whether the antinociceptive properties of morphine and neurotensin (NT) are dependent upon central serotonergic neurotransmission. To this end, we studied the effects of morphine (10 mg/kg i.p.) and NT (30 μ i.c.v.) on the turnover of 5-hydroxytryptamine (5-HT) in 8 microdissected nuclei of adult rat brain: n. septalis lateralis (LS); n. tractus diagonalis (DB); n. amygdaloideus centralis (AG); posterior medial forebrain bundle (MFG); periaqueductal gray (PAG); n. raphe dorsalis (DR); n. centralis superior (NCS); and n. raphe magnus (RM). The systemic administration of morphine did not alter rates of 5-hydroxytryptophan (5-HTP) biosynthesis in anu of the nuclei examined, although concentrationsof serotonin were increased by 24% in the RM. In contrast, the central administration of neurotensin significantly decreased the rate of 5-HTP biosynthesis in the posterior MFB. The central administration of NT was accompanied by increased levels of serotonin in the DB, DR, and RM and by decreased serotonin levels in the MFB and PAG. In a complementary series of experiments, the effect of depletion of central 5-HT stores on the antinociceptive properties of both morphine and NT was determined.p-Chlorophenylalinine (PCPA, 325 mg/kg, i.p.) decreased whole brain 5-HT levels by 87%, but had no effect upon the increase in hot plate latencies induced by morphine.Conversely, although without significant antinociceptive properties of its own, PCPA markedly potentiated the antinociceptive effects of NT. From these results, 3 conclusions appear warranted: (1) the antinociceptive effects of NT and morphine may each depend upon differing neuronal pathways within the CNS; (2) the (3) the activity of ascending serotonergic fibers in the posterior medial forebrain bundle may be involved in NT-induced antinociception. (3) the activity of ascending serotonergic fibers in the posterior medial forebrain bundle may be involved in NT-induced antinociception.