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Evidence that m‐chlorophenylpiperazine inhibits some nociceptive responses of rats by activating 5‐hydroxytryptamine mechanisms

Several studies suggest that 5-hydroxytryptamine (5-HT) in the central nervous system (c.n.s.) acts by inhibiting animal responses to painful stimuli. The evidence is based mainly on experiments using lesions or stimulation of 5-HTcontaining neurons or direct administration of 5-HT into various areas of the c.n.s. (Samanin et a1 1970; Samanin & Valzelli 1971; Oliveras et a1 1975; Messing & Lytle 1977; Sewell & Spencer 1977; Yaksh & Wilson 1979). There is some controversy about whether drugs increasing 5-HT transmission have antinociceptive effects when administered systemically. Quipazine, a 5-HT agonist (Jacoby et a1 1976) was found by Samanin et a1 (1976) to inhibit nociceptive responses of rats in the hot plate and tail compression tests. However, other authors failed to find any effect of quipazine in the hot plate test (Malec & Langwinski 1980). More recently, quipazine was found to reduce rat responses in the hot plate but not in the tail flick test (Minnema et al 1980). There are also some differences about the ability of 5-HT uptake inhibitors to cause antinociception in rats (Messing et a1 1975; Larson & Takemori 1977). There is no clear explanation for the different results, although differences in the antinociceptive tests may play a major role (Ogren & Holm 1980; Dennis & Melzack 1980). m-Chlorophenylpiperazine (mCPP), which displaces PHI5-HT bound to brain membranes (Samanin et a1 1979; Fuller et a1 1981) and has behavioural and biochemical effects compatible with a stimulatory action on 5-HT receptors (Samanin et a1 1979), has been examined for its effects on various nociceptive responses of rats and to assess whether these depend on its effect on 5-HT.