European Journal of Pharmacology, 86 (1983) 65-70 65 Elsevier Biomedical Press ROLE OF 5-HT AND NA IN SPINAL DOPAMINERGIC ANALGESIA TROELS S. JENSEN * and DONALD F. SMITH ** Department of Neurology, A arhus University Hospital, DK-8000 A arhus C, and ** The PsI'chopharmacological Research Unit. A arhus University Institute of Psychiatry, Psychiatric Hospital, DK-8240 Risskov. Denmark Received 11 June 1982, revised MS 25 August 1982. accepted 16 September 1982 T,S. JENSEN and D.F. SMITH, Role of 5-HT and NA in spinal dopaminergic analgesia, European J. Pharmacol. 86 (1983) 65-70. Spinal rats and rats with an intact neuraxis given the dopamine (DA) agonist R-apomorphine (0.31-1.75 Fmol/kg) in the lumbar subarachnoid space by intrathecal injection were tested 5 and 10 min later for spinal analgesia (increased tail-flick response latency). Apomorphine produced analgesia in spinal rats but not in rats with an intact neuraxis. However, pretreatment of intact rats with the serotonergic (5-HT) receptor antagonist methysergide, the noradrenergic (NA) receptor antagonist phentolamine or the two antagonists together led to a dose-dependent analgesia following apomorphine. Intact rats pretreated with the monoamine depleting drug reserpine, the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) or the NA synthesis inhibitor FLA 63 also showed analgesia to apomorphine. On the other hand, pretreatment with the catecholamine depleting agent a-methyl-p-tyrosine (AMPT), the J3-adrenergic receptor blocker propranolol or the opioid receptor antagonist naloxone failed to produce DA analgesia. The present findings suggest that both 5-HT and NA descending fiber systems exert tonic inhibitory effects on spinal DA nociceptive processes. Apomorphine DA spinal analgesia Noradrenaline Serotonin Supraspinal control 1. Introduction Monoaminergic mechanisms are involved in the spinal control of nociception (Engberg and Ryall, 1966; Belcher et al., 1978; Headley et al., 1978; Fields and Basbaum, 1978; Zemlan et al., 1980; Hodge et al., 1981; Tyce and Yaksh, 1981). The present report focusses on the role of spinal cord dopamine (DA) in nociceptive processes. Previ- ously, we reported that intrathecal (i.t.) infusion of the DA agonist R-apomorphine (And6n et al., 1967; Ernst, 1967) caused analgesia as measured in the tail-flick test in spinal rats, and that this effect was counteracted stereoselectively by DA antago- nists but not by serotonergic (5-HT) or noradrenergic (NA) antagonists (Jensen and Smith, * To whom all correspondence should be addressed: Depart- ment of Neurology, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. 0014-2999/83/0000-0000/$03.00 © 1983 Elsevier Biomedical Press 1982). Our findings indicate that DA may play a role in spinal nociceptive processes. On the other hand, we found that i.t. infusion of apomorphine had no analgesic effect in rats with an intact neuraxis. These findings suggested to us that de- scending neuronal pathways inhibit spinal DA- ergic mechanisms. To test this possibility we have carried out experiments to determine whether blockade of 5-HT and/or NA neurotransmission led to spinal DA-ergic analgesia in rats with an intact neuraxis. 2. Materials and methods 2.1. Animals Male Wistar rats weighing 275-325 g were used. They were kept individually in clear plastic cages in a thermostatically controlled room (20°C) on a