Abstract
The effects of para-chlorophenylalanine pre-treatment (PCPA, 150 mg/kg IP daily for 3 days) on feeding and stereotyped behaviour elicited by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in rats were investigated. PCPA depleted brain serotonin and 5-hydroxyindoleacetic acid concentrations by 90% and increased feding during a 2-h day-time test. 8-OH-DPAT (60–4000 μg/kg SC) increased food intake in control animals but decreased in in PCPA-treated animals during the 2-h test. PCPA treatment had no effect on 8-OH-DPAT-induced locomotion or serotonin-related stereotyped behaviour (i.e. forepaw treading, headweaving, wet dog shakes, etc). Since PCPA prevents the operation of pre-synaptic serotonergic mechanisms, the failure of 8-OH-DPAT to increase food intake in PCPA-treated rats suggests that 8-OH-DPAT-induced hyperphagia is autoreceptor mediated.
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Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, Wikstrom H, Sanchez D Arvidsson L.-E, Hacksell U, Nilsson JLG (1981) Effects of a new type of 5-HT receptor agonist on male rat sexual behaviour. Pharmacol Biochem Behav 15:785–792
Arvidsson L-E Hacksell U, Nilsson JLG, Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H (1981) 8-Hydroxy-2-(di-n-propylamino) tetralin, a new centrally acting 5-HT receptor agonisn. J Med Chem 24:921–923
Blundell JE (1984) Systems and interactions: an approach to the pharmacology of eating and hunger. In: Stunkard AJ, Stellar E Eating and its disorders. Raven Press, New York, pp 39–65
Dourish CT, Hutson PH, Curzon G (1985a) Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology 86:197–204
Dourish CT, Hutson PH, Curzon G (1985b) Characteristics of feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Brain Res Bull 15:377–384
Dourish CT, Hutson PH, Kennett GA, Curzon G (1986a) 8-OH-DPAT-induced hyperphagia: its neural basis and possible therapeutic relevance. Appetite (in press)
Dourish CT, Hutson PH, Curzon G (1986b) The novel putative anxiolytics 8-OH-DPAT, buspirone and TVXQ 7821 are agonists at 5-HT1A autoreceptors in the raphe nuclei. TIPS (in press)
Engel JA, Hjorth S, Svensson K, Carlsson A, Liljequist S (1984) Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Eur J Pharmacol 105:365–368
Ferron A, Descarries L, Reader TA (1982) Altered neuronal responsiveness to biogenic amines in rat cerebral cortex after serotonin denervation or depletion. Brain Res 231:93–108
Gessa GL, Tagliamonte A (1974) Role of brain monoamines in male sexual behaviour. Life Sci 14:425–436
Gozlan H, El Mestikawy S, Pichat L, Glowinski J, Hamon M (1983) Identification of presynaptic serotonin autoreceptors using a new ligand:3H-PAT. Nature 305:140–142
Hamon M, Bourgoin S, Gozlan H, Hall MD, Goetz G, Artaud F, Horn AS (1984) Biochemical evidence for the 5-HT agonist properties of PAT (8-hydroxy-2(di-n-propylamino)tetralin) in the rat brain. Eur J Pharmacol 100:263–276
Hendrie CA, Bennett S (1983) A microcomputer technique for the detailed analysis of animal behaviour. Physiol Behav 30:233–235
Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikstrom H, Arvidsson L-E, Hacksell U, Nilsson JLG (1982) 8-Hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent and selective simplified ergot congener with central 5-HT receptor stimulating activity. J Neural Transm 55:169–188
Koe B, Weissman A (1966)p-Chorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516
Middlemiss DN (1984) 8-hydroxy-2-(di-n-propylamino)tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H] 5-HT recognition site. Naunyn Schmiedeberg's Arch Pharmacol 327:18–22
Robbins TW (1981) Behavioural determinants of drug action: ratedependency revisited. In: Cooper SJ Theory in psychopharmacology. London, Academic Press, pp 1–63
Tricklebank MD Forler C, Fozard JR (1984) The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat Eur J Pharmacol 106:271–282
Trulson ME, Eubanks EE, Jacobs BL (1976) Behavioural evidence for supersensitivity following destructruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine. J Pharmacol Exp Ther 198:23–32
Verge D, Daval G, Patey A Gozlan H, El Mestikawy S, Hamon M (1985) Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are on the 5-HT1A subtype. Eur J Pharmacol 113:463–464
Wang RY, deMontigny C, Gold BI, Roth RH, Aghajanian GK (1979) Denervation supersensitivity to serotonin in rat forebrain: single cell studies. Brain Res 178:479–497
Weissman A, Harbert CA (1972) Recent developments relating serotonin and behaviour. Ann Rep Med Chem 7:47–58
Weissman-Nanopoulos D, Mach E Magre J, Demassey Y, Pujol JF (1985) Evidence for the localisation of 5-HT1A binding sites on serotonin containing neurons in the raphe dorsalis and raphe centralis nuclei of the rat brain. Neurochem Int 7:1061–1072
Winer BJ (1971) Statistical principles in experimental design. McGraw Hill, New York
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Dourish, C.T., Hutson, P.H. & Curzon, G. Para-chlorophenylalanine prevents feeding induced by the serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT). Psychopharmacology 89, 467–471 (1986). https://doi.org/10.1007/BF02412123
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DOI: https://doi.org/10.1007/BF02412123