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Dopamine autoreceptors in the ventral tegmental area show subsensitivity following withdrawal from chronic antidepressant drug treatment

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Abstract

The suppression by apomorphine of food intake and eating time was used to assay the sensitivity of dopamine cell body autoreceptors during the course of treatment with DMI, amitriptyline and mianserin. Brief (2–4 days) DMI treatment enhanced the effects of apomorphine, administered systemically or centrally to DA cell body regions. During chronic DMI treatment (3–7 weeks) some evidence of autoreceptor subsensitivity was observed with systemic apomorphine, but not with central apomorphine. Responses to apomorphine applied systemically were reduced during withdrawal from chronic DMI, and responses to apomorphine applied to the ventral tegmental area were reduced during withdrawal from all three antidepressants. As evidence of DA autoreceptor subsensitivity was only observed reliably during withdrawal, this effect is unlikely to be of clinical importance.

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References

  • Bannon MJ, Reinhard Jr JF, Bunney EB, Roth RH (1982) Unique response to antipsychotic drugs is due to absence of terminal autoreceptors in mesocortical dopamine neurones. Nature 296:444–446

    Google Scholar 

  • Bunney BS, Aghajanian GK (1976) d-amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striatonigral feedback pathway. Science 192:391–393

    Google Scholar 

  • Carlsson A (1975) Dopaminergic autoreceptors. In: Almgren O, Carlsson A, Engel L (eds) Chemical tools in catecholamine research, vol II. Marcel Dekker, New York, pp 49–65

    Google Scholar 

  • Chiodo LA, Antelman SM (1980) Repeated tricyclics induce a progressive dopamine autoreceptor subsensitivity independent of daily drug treatment. Nature 287:451–454

    Google Scholar 

  • Di Chiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–566

    Google Scholar 

  • Divac I (1972) Drug-induced syndromes in rats with large lesions in the corpus striatum. Psychopharmacology 17:171–178

    Google Scholar 

  • Flemenbaum A (1979) Failure of apomorphine to induce dopamine receptor hypersensitivity. Psychopharmacology 62:175–179

    Google Scholar 

  • Gordon D, Beck C (1984) Subacute apomorphine injections in rats: effects on components of behavioural stereotypy. Behav Neural Biol 41:200–208

    Google Scholar 

  • Halaris A, Belendiuk K, Freedman DX (1975) Antidepressant drugs affect dopamine re-uptake. Biochem Pharmacol 24:1896–1898

    Google Scholar 

  • Hjorth S, Carlsson A, Clark D, Svensson D, Wikstrom H, Sanchez D, Lindberg P, Hacksell U, Arvidsson L-E, Johansson A, Nilsson JLG (1982) In: Carlsson A, Nilsson JLG (eds) Pharmacological manipulation of central dopamine (DA) autoreceptor agonists. Acta Pharmaceutica Swedica Suppl. 1983:1. Swedish Pharmaceutical Press, Stockholm, pp 130–137

    Google Scholar 

  • Holcomb HH, Bannon MJ, Roth RH (1982) Striatal dopamine autoreceptors uninfluenced by chronic administration of anti-depressants. Eur J Pharmacol 82:173–178

    Google Scholar 

  • Hytell J (1978) Inhibition of [3H] dopamine accumulation in rat striatal synaptosomes by psychotropic drugs. Biochem Pharmacol 27:1063–1068

    Google Scholar 

  • Kadzielawa K, Popielarski M (1971) Potentiation by desipramine of the pressor and depressor effects of dopamine. J Pharm Pharmacol 30:159–163

    Google Scholar 

  • MacNeill DA, Gower M (1982) Do antidepressants induce dopamine autoreceptor subsensitivity? Nature (Lond) 298:302

    Google Scholar 

  • Maj J, Pawlowski L, Wiszniowska G (1970) The effect of tricyclic antidepressants on apomorphine-induced hypothermia in the mouse. Pol J Pharmacol Pharm 26:329–336

    Google Scholar 

  • Menge HG, Brand V (1971) Untersuchungen über die Stereotypien nach Amphetamin und Apomorphine sowie deren pharmakologische Beeinflussung. Psychopharmacologia 21:212–228

    Google Scholar 

  • Molander L, Randrup A (1976) Effects of thymoleptics on behaviour associated with changes in brain dopamine. II. Modification and potentiation of apomorphine-induced stimulation of mice. Psychopharmacology 49:139–144

    Google Scholar 

  • Muscat R, Willner P, Towell A (1986) Apomorphine anorexia: A further pharmacological characterisation. Eur J Pharmacol (in press)

  • Pellegrino LJ, Cushman AJ (1967) A stereotaxic atlas of the rat brain. Appleton-Century-Crofts, New York

    Google Scholar 

  • Puech AJ, Chermat R, Poncelet M, Doare L, Simon P (1981) Antagonism of hypothermia and behavioural response to apomorphine: a simple, rapid and discriminating test for screening antidepressants and neuroleptics. Psychopharmacology 75:84–91

    Google Scholar 

  • Reches A, Wagner HR, Barkai AI, Jackson V, Yablouskaya-Alter E, Fahn S (1984) Electroconvulsive treatment and haloperidol: Effects on pre-and post-synaptic dopamine receptors in rat brain. Psychopharmacology 83:155–158

    Google Scholar 

  • Schelkunov EL (1980) Action of neuroleptics and antidepressants on the hypothermia produced by dopaminomimetics, apomorphine and piribedil in mice. J Neural Transm 47:307–312

    Google Scholar 

  • Serra G, Argiolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevents the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25:415–424

    Google Scholar 

  • Skirboll LR, Grace AA, Bunney BS (1979) Dopamine auto-and postsynaptic receptors: Electrophysiological evidence for differential sensitivity to dopamine agonists. Science 206:80–82

    Google Scholar 

  • Spyraki C, Fibiger HC (1981) Behavioural evidence for supersensitivity of postsynaptic dopamine receptors in the mesolimbic system after chronic administration of desipramine. Eur J Pharmacol 74:195–206

    Google Scholar 

  • Towell A, Muscat R, Willner P (1986) Apomorphine anorexia: the role of dopamine cell body autoreceptors. Psychopharmacology (in press)

  • Wang RY (1981) Dopaminergic neurons in the rat ventral tegmental area. II. Evidence for autoregulation Brain Res Rev 3:141–151

    Google Scholar 

  • Willner P (1983) Dopamine and depression: A review of recent evidence. III. The effects of antidepressant treatments. Brain Res Rev 6:237–246

    Google Scholar 

  • Willner P, Towell A (1982) Microstructural analysis of the involvement of beta-receptors in amphetamine anorexia. Pharmacol Biochem Behav 17:255–262

    Google Scholar 

  • Willner P, Towell A, Muscat R (1985) Apomorphine anorexia: a behavioural and neuropharmacological analysis. Psychopharmacology 87:351–356

    Google Scholar 

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Towell, A., Willner, P. & Muscat, R. Dopamine autoreceptors in the ventral tegmental area show subsensitivity following withdrawal from chronic antidepressant drug treatment. Psychopharmacology 90, 64–71 (1986). https://doi.org/10.1007/BF00172873

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  • DOI: https://doi.org/10.1007/BF00172873

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