Quipazine reduces food intake in the rat by activation of 5‐HT₂‐receptors

Abstract

1 To determine which subtype(s) of 5-hydroxytryptamine (5-HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5-HT2-and 5-HT3-receptors, and an antagonist at 5-HT1-like receptors, to block this response were investigated in non-deprived rats, trained to eat a palatable diet. 2 Quipazine (0.5-8mg kg-, i.p.) produced a dose-related reduction in the intake of palatable diet. 3 The anorectic effect of 4 mg kg1 quipazine was antagonized by the nonselective 5-HT-receptor antagonist methysergide (5 mg kg 1, i.p.) and by the selective 5-HT2-receptor antagonists ketanserin (1mgkg-1 and 2.5mgkg-1, i.p.) and ritanserin (0.5mgkg-1 and lmgkg-1, i.p.). The selective 5-HT3-receptor antagonist GR38032F (1mgkg-1, i.p.) and (-)-pindolol (4mgkg-, i.p.), which blocks some of the effects mediated at 5-HT1-like receptors, did not block the reduction in food intake produced by this dose of quipazine. 4 None of the 5-HT-receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5-HT is not involved in the tonic control of food intake under the conditions of these experiments. 5 It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5-HT2-receptors.

Potencies of antagonists indicate that 5‐HT1C receptors mediate 1–3(chlorophenyl)piperazine‐induced hypophagia

“…The failure of Aulakh et al (1989) (and RU 24969) and hence possibly also to their antagonists, than when food-deprived animals are used as in the present study (Table 3). A similar argument may also explain why doses of ketanserin and ritanserin needed to antagonize hypophagias induced by fenfluramine (Hewson et al, 1988), quipazine (Hewson et al, 1989) and DOI (Schechter & Simansky, 1988) were less than those we found to inhibit Kennett et al (1987) and Kennett & Curzon (1988a) expressed as percentages and Arcsin-transformed (Winer, 1971) as outlined by Bowman & Rand (1980). mCPP-induced hypophagia as these groups used fed rats exposed to a palatable diet.…”

“…It is also relevant that the doses of ketanserin and ritanserin required for inhibition of hypophagia were much greater than those we found necessary for inhibition of 5-HT2 receptor-mediated head shakes. Furthermore, Neill & Cooper (1989) did not confirm the inhibitory effect of ketanserin on fenfluramine-induced hypophagia reported by Hewson et al (1988).…”

“…The inability of ritanserin to antagonize completely mCPPinduced hypophagia was striking; rather similar but less detailed findings are reported for the inhibition of quipazineinduced hypophagia by both ritanserin and ketanserin (Hewson et al, 1989) and for the inhibition of fenfluramineinduced hypophagia by ritanserin (Neill & Cooper, 1989). Partial inhibition could conceivably be due to the ritanserin being a partial agonist but this seems unlikely as it did not cause hypophagia when given alone.…”

“…Thus the effects of antagonists on hypophagias induced by the 5-hydroxy- ' Author for correspondence at present address: Smith Beecham Pharmaceuticals, The Pinnacles, Harlow, Essex. tryptamine (5-HT) releasing agent fenfluramine (Hewson et al, 1988), the 5-HT1J5-HT2 agonists DOI (Schechter & Simansky, 1988) and quipazine (Hewson et al, 1989) have all been interpreted in terms of activation of 5-HT2 receptors. Also, other reports suggest that the effect of TFMPP is 5-HT2-mediated (Klodzinska & Chojnacka-Wojcik, 1990) and that the action of mCPP might not be 5-HT1c-dependent (Aulakh et al, 1989).…”

Serotonergic modulation of the discriminative-stimulus effects of cocaine in squirrel monkeys

“…A variety of 5-HT 2 -selective agonists can exert stimulus control over behavior (Glennon 1991;Ismaiel et al 1993), and 5-HT 2 -selective agonists substitute for quipazine, whereas 5-HT 2 -selective antagonists readily block quipazine discrimination (Glennon et al 1983;Friedman et al 1984;Smith et al 1995). Moreover, studies have demonstrated 5-HT 2 receptor involvement in quipazine-induced suppression of schedule-controlled operant behavior in squirrel monkeys (McKearney 1990), and in quipazine-induced anorexia in rodents (Hewson et al 1988;Skukla et al 1990). In addition to serotonergic mechanisms, limited evidence indicates that DA could contribute to the discriminative-stimulus effects of quipazine.…”