Restricted accessResearch articleFirst published online 1991-3
Long-term administration of m-chlorophenylpiperazine to rats does not alter functional sensitivity of either pre-synaptic or postsynaptic 5-HT1A receptors
Administration of the selective 5-HT1A agonist, 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT ), to rats produced increases in food intake in freely fed animals and decreases in food intake in food-deprived animals. Acute pre-treatment with various doses of m-chlorophenylpiperazine (m-CPP, another 5-HT agonist) attenuated 8-OHDPAT-induced increases in food intake in the free-feeding paradigm and enhanced 8- OHDPAT-induced decreases in food intake in the food-deprived paradigm. In the two paradigms, however, neither increases nor decreases in food intake induced by 8-OHDPAT were altered in animals following long- term (21-day) treatment with m-CPP versus saline when animals were challenged with 8-OHDPAT 48 h after the last dose of m-CPP. These findings suggest that long-term m-CPP treatment does not alter the functional sensitivity of 5-HT1A receptors located pre-synaptically that mediate hyperphagia or 5-HT1A receptors located post-synaptically that mediate decreases in food intake by induction of the serotonin behavioural syndrome.
Get full access to this article
View all access options for this article.
References
1.
Aulakh C.S., Wozniak K.M., Haas M., Hill J.L., Zohar J., Murphy D.L. (1988) Food intake, neuroendocrine and temperature effects of 8-OHDPAT in the rat. Eur J Pharmacol146: 253-259
2.
Bendotti C., Samanin R. (1986) 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicits eating in free-feeding rats by acting on central serotonin neurons . Eur J Pharmacol121: 147-150
3.
Bendotti C., Samanin R. (1987) The role of putative 5-HT1A and 5-HT 1B receptors in the control of feeding in rats. Life Sci41: 635—642
4.
Caccia S., Ballabio M., Samanin R., Zanini M.G., Garattini S. (1981) (—)-m-Chlorophenylpiperazine, a central 5-hydroxytryptamine agonist, is a metabolite of trazodone. J Pharm Pharmacol33: 477-478
5.
Cervo L., Grignaschi G., Samanin R. (1988) 8-Hydroxy-2-(din-propylamino)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis. Eur J Pharmacol158: 53-59
6.
De Souza R.J., Goodwin G.M., Green A.R., Heal D.J. (1986) Effect of chronic treatment with 5-HT1 agonist (8-OHDPAT and RU 24969) and antagonist (isapirone) drugs on the behavioural responses of mice to 5-HT1 and 5-HT2 agonists. Br J Pharmacol89: 377-384
7.
Dourish C.T., Hutson P.H., Curzon G. (1985) Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT ) elicit feeding in the rat. Psychopharmacology86: 197-204
8.
Fuller R.W., Snoddy H.D., Mason N.R., Owens J.E. (1981) Disposition and pharmacological effects of m-chlorophenylpiperazine in rats. Neuropharmacology20: 155-162
9.
Goodwin G.M., De Souza R.J., Green A.R. (1985) The pharmacology of the hypothermic response in mice to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT): A model of presynaptic 5-HT1 function. Neuropharmacology24: 1187-1194
10.
Hamon M., Cossery J.M., Spampinato U., Gozlan H. (1986) Are there selective ligands for 5-HT1A and 5-HT1B receptor binding sites in brain?Trends Pharmacol Sci7: 336-338
11.
Hjorth S., Carlsson A., Lindberg P., Sanchez D., Wikstrom H., Arvidsson L.E., Hacksell U., Nilsson J L G (1982) 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OHDPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity. J Neural Transm55: 169-188
12.
Hoyer D. (1988) Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res8: 59-81
13.
Hutson P.H., Dourish C.T., Curzon G. (1986) Neurochemical and behavioural evidence for mediation of the hyperphagic action of 8-OH-DPAT by 5-HT cell body autoreceptors. Eur J Pharmacol129: 347-352
14.
Kennett G.A., Curzon G. (1988) Evidence that m-CPP may have behavioral effects mediated by central 5-HT1C receptors. Br J Pharmacol94: 137-147
15.
Kennett G.A., Dourish C.T., Curzon G. (1987a) 5-HT1B agonists induce anorexia at a postsynaptic site. Eur J Pharmacol141: 429-435
16.
Kennett G.A., Dourish C.T., Curzon G. (1987b) Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression . Eur J Pharmacol134: 265-274
17.
Mellow A.M., Lawlor B.A., Sunderland T., Mueller E.A., Molchan S.E., Murphy D.L. (1990) Effects of daily oral m-chlorophenylpiperazine in elderly depressed patients. Initial experience with a serotonin agonist . Biol Psychiat28: 588-594
18.
Middlemiss D.N., Fozard J.R. (1983) 8-Hydroxy-2-(di-n-propylamino)tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol90: 151-153
19.
Murphy D.L., Mueller E.A., Hill J.L., Tolliver T.J., Jacobsen F.M. (1989) Comparative anxiogenic, neuroendocrine, and other physiologic effects of m-chlorophenylpiperazine given intravenously or orally to healthy volunteers. Psychopharmacology98: 275-282
20.
Rurak A., Melzacka M. (1983) Effect of dosage and route of administration of trazodone on cerebral concentration of 1-m-chlorophenylpiperazine in rats: Kinetics of trazodone biotransformation in ratsPol J Pharmacol Pharm35: 241-247
21.
Samanin R., Mennini T., Ferraris A., Bendotti C., Borsini F., Garattini S. (1979) M-chlorophenylpiperazine: A central serotonin agonist causing powerful anorexia in rats. Naunyn Schmiedebergs Arch Pharmacol308: 159-163
22.
Sills M.A., Lucki I., Frazer A. (1985) Development of selective tolerance to the serotonin behavioral syndrome and suppression of locomotor activity after repeated administration of either 5-MeODMT or m-CPP. Life Sci36: 2463-2469
23.
Sills M.A., Wolfe B.B., Frazer A. (1984) Determination of selective and nonselective compounds for the 5-HT1A and 5-HT1B receptor subtypes in rat frontal cortexJ Pharmacol Exp Ther231: 480-487
24.
Tricklebank M.D., Forler C., Fozard J.R. (1985) 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 ratEur J Pharmacol106: 271-282
25.
Tricklebank M.D., Middlemiss D.N., Neill J. (1986) Pharmacological analysis of the behavioral and thermoregulatory effects of the putative 5-HT1 receptor agonist, RU-24969, in the rat. Neuropharmacology25: 877-886
