Skip to main content
SpringerLink
Log in

Behavioural changes during withdrawal from desmethylimipramine (DMI)

I. Interactions with amphetamine

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Amphetamine anorexia in rats was potentiated by acute pretreatment with the tricyclic antidepressant desmethylimipramine (DMI), but was not significantly different from controls following chronic DMI pretreatment. During withdrawal from DMI, amphetamine anorexia was attenuated after 2 weeks or 2 months pretreatment, but not after 1 week of treatment. The locomotor stimulant and stereotypy inducing effects of amphetamine were slightly enhanced during withdrawal from chronic DMI. The results are discussed in relation to known neurochemical actions of DMI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahlskog JE (1974) Food intake and amphetamine anorexia after selective forebrain norepinephrine loss. Brain Res 82:211–240

    Google Scholar 

  • Ahlskog JE, Hoebel BG (1973) Overeating and obesity from damage to a noradrenergic system in the brain. Science 182:166–169

    Google Scholar 

  • Banerjee SP, Kung LS, Riggi SJ, Chanda SK (1977) Development of β-adrenergic receptor subsensitivity by antidepressants. Nature 268:455–456

    Google Scholar 

  • Bloom FE, Siggins GR, Schultz JE, Henriksen SJ (1979) Catecholamine transmitter systems. In: Schoolar JL, Claghorn JL (eds) The kinetics of psychiatric drugs, Brunner/Mazel, New York, pp 63–75

    Google Scholar 

  • Bradshaw CM, Roberts MHT, Szabadi E (1974) Effects of imipramine and desipramine on responses of single cortical neurons to noradrenaline and 5-hydroxytryptamine. Br J Pharmacol 52:349–358

    Google Scholar 

  • Canguilhem B, Schmitt P, Mack G, Kempf E (1977) Comportement alimentaire, rythmes circannuel pondéral et d'hibernation chez le hamster d'Europe porteur de lésions des faisceaux noradrénergiques ascendants. Physiol Behav 18:1067–1074

    Google Scholar 

  • Cole SO (1972) The relationship of amphetamine-induced anorexia and freezing under free-feeding conditions. Pharmacol Res Commun 4:71–76

    Google Scholar 

  • Consolo S, Dolfini E, Garattini S, Valzelli L (1967) Desipramine and amphetamine metabolism. J Pharm Pharmacol 19:253–256

    Google Scholar 

  • Creese I, Iversen SD (1973) Blockade of amphetamine induced motor stimulation and stereotypy in the adult rat following neonatal treatment with 6-hydroxydopamine. Brain Res 55:369–382

    Google Scholar 

  • Creese I, Iversen SD (1974) The role of forebrain dopamine systems in amphetamine induced stereotyped behaviour in the rat. Psychopharmacology 39:345–357

    Google Scholar 

  • Frazer A, Mendels J (1977) Do tricyclic antidepressants enhance adrenergic transmission? Am J Psychiatry 134:1041–1042

    Google Scholar 

  • Garattini S, Borroni E, Mennini T, Samanin R (1978) Differences and similarities among anorectic agents. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, pp 127–143

    Google Scholar 

  • Glowinski J, Axelrod J (1964) Inhibition of the uptake of tritiated noradrenaline in the intact rat brain by imipramine and structurally related compounds. Nature 204:1318–1319

    Google Scholar 

  • Gluckman MI, Baum T (1969) The pharmacology of iprindole, a new antidepressant. Psychopharmacology 15:169–185

    Google Scholar 

  • Hoebel BG (1979) Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating. Fed Proc 36:2454–2461

    Google Scholar 

  • Huang YH (1979) Chronic desipramine treatment increases activity of noradrenergic postsynaptic cells. Life Sci 25:709–716

    Google Scholar 

  • Jespersen S, Scheel-Kruger J (1973) Evidence for a difference in mechanism of action between fenfluramine- and amphetamine-induced anorexia. J Pharm Pharmacol 25:49–54

    Google Scholar 

  • Kelly PH (1977) Drug induced motor behaviour. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol. 8. Plenum Press, New York and London, pp 295–331

    Google Scholar 

  • Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 24:507–522

    Google Scholar 

  • Kruk ZL, Millar J (1979) The effect of bilateral ventral noradrenaline bundle lesions on lever pressing for food in rats. Psychopharmacology 64:41–43

    Google Scholar 

  • Leibowitz SF (1975) Catecholaminergic mechanisms of the lateral hypothalamus: their role in the mediation of ampetamine anorexia. Brain Res 98:529–545

    Google Scholar 

  • Leibowitz SF (1978) Identification of catecholamine receptor mechanisms in the perifornical lateral hypothalamus and their role in mediating amphetamine and 1-DOPA anorexia. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, pp 39–82

    Google Scholar 

  • Leibowitz SF, Rossakis C (1978) Analysis of feeding suppression produced by perifornical hypothalamic injection of catecholamines, amphetamine and mazindol. Eur J Pharmacol 53:69–81

    Google Scholar 

  • Lemberger L, Sernatinger E, Kuntzman R (1970) Effect of desmethylimipramine, iprindole and DL-erythro-α (3,4-dichlorophenyl)-β-(t-butyl amino) propanol HCl on the metabolism of amphetamine. Biochem Pharmacol 19:3021–3028

    Google Scholar 

  • Lewander T (1968) Effects of amphetamine on urinary and tissue catecholamines in rats after inhibition of its metabolism with desmethylimipramine. Eur J Pharmacol 5:1–9

    Google Scholar 

  • Lorden J, Oltmans GA, Margules DL (1976) Central noradrenergic neurons: differential effects on body weight of electrolytic and 6-hydroxydopamine lesions in rats. J Comp Physiol Psychol 90:144–155

    Google Scholar 

  • Maggi A, U'Prichard DC, Enna SJ (1980) Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmacol 61:91–98

    Google Scholar 

  • Mason ST, Iversen SD (1979) Theories of the dorsal bundle extinction effect. Brain Res Rev 1:107–137

    Google Scholar 

  • McMillen BA, Warnack W, German DC, Shore PA (1980) Effects of chronic desipramine treatment on rat brain noradrenergic responses to α-adrenergic drugs. Eur J Pharmacol 61:239–246

    Google Scholar 

  • Menon MK, Subramanian K, Menon NK, Sharma SN (1970) Influence of desmethylimipramine on the appetite-lowering effects of d-amphetamine and other anorectics. Eur J Pharmacol 12:156–160

    Google Scholar 

  • Modell W (1960) Status and prospects of drugs for overeating. JAMA 173:1132–1136

    Google Scholar 

  • Oltmans GA, Lorden JF, Margules DL (1977) Food intake and body weight: effects of specific and non-specific lesions in the midbrain path of the ascending noradrenergic neurons of the rat. Brain Res 128:293–308

    Google Scholar 

  • Pijenburg AJJ, Honig WMM, Rossum JM van (1975) Inhibition of d-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat. Psychopharmacology 41:87–95

    Google Scholar 

  • Raisman R, Briley M, Langer SZ (1979) High affinity 3H-imipramine binding in rat cerebral cortex. Eur J Pharmacol 54:307–308

    Google Scholar 

  • Roffler-Tarlov S, Schildkraut JJ, Draskoczy PR (1973) Effects of acute and chronic administration of desmethylimipramine on the content of norepinephrine and other monoamines in the rat brain. Biochem Pharmacol 22:2923–2926

    Google Scholar 

  • Rosloff BN, Davis JD (1978) Decrease in brain NE turnover after chronic DMI treatment; no effect with iprindole. Psychopharmacology 56:335–341

    Google Scholar 

  • Samanin R, Bendotti C, Bernasconi S, Pataccini R (1978) Differential role of brain monoamines in the activity of anorectic drugs. In: Garattini S, Samanin R (eds) Central mechanisms of anorectic drugs. Raven Press, New York, pp 233–242

    Google Scholar 

  • Sanghvi IS, Singer G, Friedman E, Gershon S (1975) Anorexigenic effects of d-amphetamine and 1-DOPA in the rat. Pharmacol Biochem Behav 3:81–86

    Google Scholar 

  • Schildkraut JJ (1975) Norepinephrine metabolism after short- and long-term administration of tricyclic antidepressant drugs and electroconvulsive shock. In: Mandell AJ (ed) Neurobiological mechanisms of adaptation and behaviour. Raven Press, New York, pp 137–153

    Google Scholar 

  • Schildkraut JJ, Winokur A, Applegate CW (1970) Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine. Science 168:867–869

    Google Scholar 

  • Schultz J (1976) Psychoactive drug effects on a system which generates cyclic AMP in Brain. Nature 261:417–418

    Google Scholar 

  • Segal DS, Kuczenski R, Mandell AJ (1974) Theoretical implications of drug-induced adaptive regulation for a biogenic amine hypothesis of affective disorder. Biol Psychiatry 9:147–159

    Google Scholar 

  • Sigg EB, Soffer L, Gyermek L (1963) Influence of imipramine and related psychoactive agents on effects of 5-hydroxytryptamine and catecholamines on the cat nictitating membrane. J Pharmacol Exp Ther 142:13–20

    Google Scholar 

  • Sprott DA (1970) Note on Evans and Anastasio on the analysis of covariance. Psychol Bull 73:303–306

    Google Scholar 

  • Sturman G (1970) Modification by a tricyclic series of compounds of the noradrenealine effect on the cat initiating membrane. J Pharm Pharmacol 23:142–143

    Google Scholar 

  • Sulser F (1979) New perspectives on the mode of action of antidepressant drugs. TIPS 2:92–94

    Google Scholar 

  • Sulser F, Owens ML, Dingell JV (1966) On the mechanism of amphetamine potentiation by desipramine (DMI). Life Sci 5:2005–2010

    Google Scholar 

  • Svensson TH, Usdin T (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: α-receptor mediation. Science 202:1089–1091

    Google Scholar 

  • Valzelli L, Consolo S, Morpurgo C (1967) Influence of imipramine-like drugs on the metabolism of amphetamine. In: Garattini S, Dukes MNG (eds) Proceedings of the first international symposium on antidepressant drugs. International Congress Series, No 122, Exerpta Medica, Amsterdam, pp 61–69

    Google Scholar 

  • Vetulani J, Stawarz RJ, Sulser F (1976) Adaptive mechanisms of the noradrenergic cyclic AMP generating system in the limbic forebrain of the rat: adaptation to persistent changes in the availability of norepinephrine. J Neurochem 27:661–666

    Google Scholar 

  • Willner P, Montgomery T (1980) Attenuation of amphetamine anorexia in rats following subchronic treatment with a tricyclic antidepressant. Commun Psychopharm 4:101–106

    Google Scholar 

  • Willner P, Montgomery T, Bird D (1981) Behavioural changes during withdrawal from desmethylimipramine (DMI). II. Increased resistance to extinction. Psychopharmacology 75:60–64

    Google Scholar 

Download references

Author information

Author notes

  1. Tony Montgomery

    Present address: Psychological Laboratory, Downing Street, Cambridge, England

Authors and Affiliations

  1. Psychology Department, City of London Polytechnic, Old Castle Street, E1 7NT, London, England

    Paul Willner & Tony Montgomery

Authors
  1. Paul Willner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tony Montgomery
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Willner, P., Montgomery, T. Behavioural changes during withdrawal from desmethylimipramine (DMI). Psychopharmacology 75, 54–59 (1981). https://doi.org/10.1007/BF00433502

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00433502

Key words

Search

Navigation