Summary
Chronic (14 day) administration of several pharmacologically-distinct antidepressant drugs resulted in marked reductions in the serotonin2 (5-HT2)-mediated quipazine-induced head shake response which were accompanied by significant reductions in the density of cortical Β-adrenergic and 5-HT2 binding sites. Noradrenergic (DSP4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine]-induced) and serotonergic (5,7-DHT[5,7-dihydroxytryptamine]-induced) lesions either attenuated or blocked antidepressant-induced reductions in 5-HT2-mediated behavior. DSP4- and 5,7-DHT lesions did not alter the down-regulation of 5-HT2 binding sites produced by imipramine, desipramine, phenelzine or iprindole. To a large extent, the antagonism of antidepressant-induced reductions in 5-HT2-mediated behavior was coincident with the blockade of down-regulation of Β-adrenergic binding sites by both noradrenergic and serotonergic denervation. The functional interrelationship of 5-HT2 and Β-adrenergic receptors suggested by the present findings may provide insight into a common mechanism underlying the action of pharmacologically-distinct antidepressant drugs.
Similar content being viewed by others
References
Bedard P, Pycock CJ (1977) Wet-dog shake behavior in the rat: a possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16: 663–670
Biegon A, Israeli M (1988) Regionally selective increases in Β-adrenergic receptor density in the brains of suicide victims. Brain Res 442: 199–203
Blackshear MA, Sanders-Bush E (1982) Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmacol Exp Ther 221: 303–308
Brogden RN, Heel RC, Speight TM, Avery GS (1979) Nomifensine: a review of its pharmacological properties and therapeutic efficacy in depressive illness. Drugs 18: 1–24
Byerley WF, McConnell EJ, McCabe RT, Dawson TM, Grosser BI (1988) Decreased betaadrenergic receptors in rat brain after chronic administration of the selective serotonin uptake inhibitor fluoxetine. Psychopharmacology 94: 141–143
Bylund DB, Snyder SH (1976) Beta-adrenergic receptor binding in membrane preparations from mammalian brain. Mol Pharmacol 12: 568–580
Cheetham SC, Crompton MR, Katona CLE, et al (1988) Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 443: 272–280
Clements-Jewery S, Robson PA (1982) Intact 5HT neuroterminals are not required for 5-HT2 receptor down-regulation by amitriptyline. Neuropharmacology 21: 725–727
Coppen A (1967) The biochemistry of affective disorders. Br J Psychiatry 113: 1237–1264
Dooley DJ, Bittiger H, Hauser KL, Bischoff SF, Waldmeier PC (1983) Alteration of central alpha2-and beta-adrenergic receptors in the rat after DSP-4, a selective noradrenergic neurotoxin. Neuroscience 9: 889–898
Dumbrille-Ross A, Tang SW, Coscina V (1982) Lack of effect of raphe lesions on serotonin S2 receptor changes induced by amitriptyline and desmethyl-imipramine. Psychiatry Res 7: 145–151
Duncan GE, Paul IA, Harden TK, Mueller RA, Stumpf WE, Breese GR (1985) Rapid down-regulation of beta-adrenergic receptors by combining antidepressant drugs with forced swim: a model of antidepressant-induced neural adaptation. J Pharmacol Exp Ther 234: 402–408
Eison AS, Yocca FD, Gianutsos G (1988) Noradrenergic denervation alters serotonin2-mediated behavior but not serotonin2 receptor number in rats: modulatory role of beta-adrenergic receptors. J Pharmacol Exp Ther 246: 571–577
Eison AS, Eison MS, Yocca FD, Gianutsos G (1989) Effects of imipramine and serotonin-2 agonists and antagonists on serotonin-2 and beta-adrenergic receptors following noradrenergic or serotonergic denervation. Life Sci 44: 1419–1427
Fuxe K, Ogren SO, Agnati LF, Andersson K, Eneroth P (1982) Effects of subchronic antidepressant drug treatment on central serotonergic mechanisms in the male rat. In: Racagni G, Costa E (eds) Typical and atypical antidepressants: molecular mechanisms. Raven Press, New York, pp 91–107
Gerson S, Baldessarini R (1975) Selective destruction of serotonin terminals in rat forebrain by high doses of 5,7-dihydroxytryptamine. Brain Res 85: 140–145
Goodwin GM, Green AR, Johnson P (1984) 5-HT2 receptor characteristics in frontal cortex and 5-HT2 receptor-mediated head-twitch behavior following antidepressant treatment to mice. Br J Pharmacol 83: 235–242
Hall H, Ross SB, Sallemark M (1984) Effect of destruction of central noradrenergic and serotonergic nerve terminals by systemic neurotoxins on the long-term effects of antidepressants on Β-adrenoceptors and 5-HT2 binding sites in the rat cerebral cortex. J Neural Transm 59: 9–23
Kirk RE (1982) Experimental design: procedures for the behavioral sciences, 2nd edn. Brooks-Cole, Monterey Ca, pp 116–120
Leysen JE, Niemegeers CJE, van Neuten JM, Laduron P (1982) [3H]-Ketanserin (R41468) a selective3H-ligand for serotonin-2 receptor binding sites. Mol Pharmacol 21: 301–314
Lucki I, Nobler MS, Frazer A (1984) Differential actions of serotonin antagonists on two behavioral models of serotonin receptor activation in the rat. J Pharmacol Exp Ther 228: 133–139
Lucki I, Frazer A (1985) Changes in behavior associated with serotonin receptors following repeated treatment with antidepressant drugs. In: Seiden LS (ed) Behavioral pharmacology, the current status. Alan R Liss, New York, pp 339–357
Maggi A, U'Prichard DC, Enna SJ (1980) Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmacol 61: 91–98
Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin and Β-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43: 954–959
McDonald D, Stancel GM, Enna SJ (1984) Binding and function of serotonin2 receptors following chronic administration of imipramine. Neuropharmacology 23: 1265–1269
McKeith IG, Marshall EF, Ferrier IN, et al (1987) 5-HT receptor binding in post-mortem brain from patients with affective disorder. J Affect Dis 13: 67–74
Noble EP, Wurtman RJ, Axelrod J (1967) A simple and rapid method for injecting3H-norepinephrine into the lateral ventricle of the rat brain. Life Sci 6: 281–291
Ogren SO, Fuxe K, Archer T, Johansson G, Holm A-C (1982) Behavioral and biochemical studies on the effects of acute and chronic administration of antidepressant drugs on central serotonergic receptor mechanisms. In: Langer SZ, Takahashi R, Segawa T, Briley M (eds) New vistas in depression. Pergamon Press, New York, pp 11–28
Ogren SO, Fuxe K, Berge OG, Agnati LF (1983) Effects of chronic administration of antidepressant drugs on central serotonergic receptor mechanisms. In: Usdin E, Goldstein M, Friedhoff AJ, Georgotas A (eds) Frontiers in neuropsychiatric research. MacMillan, London, pp 93–108
Ogren SO, Fuxe K (1985) Effects of antidepressant drugs on cerebral serotonin receptor mechanisms. In: Green AR (ed) Neuropharmacology of serotonin. Oxford University Press, New York, pp 131–180
Pawlowski L, Melzacka M (1986) Inhibition of head-twitch response to quipazine in rats by chronic amitriptyline but not fluvoxamine or citalopram. Psychopharmacology 88: 279–284
Peroutka SJ, Snyder SH (1980) Regulation of serotonin2 (5-HT2) receptors labelled with [3H]spiroperidol by chronic treatment with the antidepressant amitriptyline. J Pharmacol Exp Ther 215: 582–586
Riva MA, Cresse I (1989a) Comparison of two putatively selective radioligands for labeling central nervous system Β-adrenergic receptors: inadequacy of [3H]dihydroalprenolol. Mol Pharmacol 36: 201–210
Riva MA, Creese I (1989b) Reevaluation of the regulation of Β-adrenergic receptor binding by desipramine treatment. Mol Pharmacol 36: 211–218
Rudeberg C (1983) Effects of single and multiple doses of antidepressant drugs on the3H-spiperone-labelled serotonin receptors in the frontal cortex of the rat. In: Usdin E, Goldstein M, Friedhoff AJ, Georgotas A (eds) Frontiers in neuropsychiatric research. MacMillan, London, pp 135–143
Scatchard GB (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672
Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122: 509–522
Stolz JF, Marsden CA, Middlemiss DN (1983) Effect of chronic antidepressant treatment and subsequent withdrawal on [3 H]-5-hydroxytryptamine and [3 H]spiperone binding in rat frontal cortex and serotonin receptor mediated behavior. Psychopharmacology 80: 150–155
Sugrue MF (1983) Chronic antidepressant therapy and associated changes in central monoaminergic receptor functioning. Pharmacol Ther 21: 1–33
Sulser F, Gillespie DD, Mishra R, Manier DH (1984) Desensitization by antidepressants of central norepinephrine receptor systems coupled to adenylate cyclase. Ann NY Acad Sci 430: 91–101
Taylor EW, Duckles SP, Nelson DL (1986) Dissociation constants of serotonin agonists in the canine basilar artery correlate to Ki values at the 5-HT1A binding site. J Pharmacol Exp Ther 236: 118–125
Wolfe BB, Harden TK, Sporn JR, Molinoff PB (1978) Presynaptic modulation of betaadrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther 207: 446–457
Wong DT, Bymaster FP, Reid LR, Threlkeld PG (1983) Fluoxetine and two other serotonin uptake inhibitors without affinity for neuronal receptors. Biochem Pharmacol 32: 1287–1293
Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5-HT2 receptor changes in major depression. Biol Psychiatry 27: 489–496
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Eison, A.S., Yocca, F.D. & Gianutsos, G. Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation. J. Neural Transmission 84, 19–32 (1991). https://doi.org/10.1007/BF01249106
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01249106