, Volume 88, Issue 2, pp 240–246 | Cite as

Effects of antidepressant drugs, selective noradrenaline-or 5-hydroxytryptamine uptake inhibitors, on apomorphine-induced hypothermia in mice

  • L. Pawłowski
  • H. Mazela
Original Investigations


Antidepressant drugs which are selective noradrenaline (NA) uptake inhibitors (desipramine, maprotiline, oxaprotiline, talsupram: 0.625–10 mg/kg) antagonized dose-dependently hypothermia induced by 16 mg/kg apomorphine (APO) in mice. Of the two stereoisomers of oxaprotiline, only that inhibiting NA uptake was active. Antidepressants which are selective 5-hydroxytryptamine (5-HT) uptake inhibitors (citalopram, fluvoxamine: 2.5–40 mg/kg) did not affect APO (16 mg/kg)-induced hypothermia. Neither NA nor 5-HT uptake inhibitors counteracted hypothermia induced by 1 mg/kg APO, a dose which is easily antagonized by low doses of dopamine receptor blockers. The antagonistic action of desipramine towards APO (16 mg/kg)-induced hypothermia was prevented by phenoxybenzamine, prazosin and (-)-propranolol, while (+)-propranolol and cyproheptidine were inactive. St 587 (an alpha1-adrenoceptor agonist) or salbutamol (an agonist of beta-adrenoceptors) attenuated APO (16 mg/kg)-induced hypothermia: given jointly, the drugs completely reversed it.m-CPP, a 5-HT receptor agonist, did not affect APO (16 mg/kg)-induced hypothermia. In conclusion, the antagonistic action of antidepressant drugs towards APO (16 mg/kg)-induced hypothermia in mice did not reflect their “antidepressant properties”, dopamine antagonism or their action on 5-HT receptors, only their effects on the NA uptake and/or NA transmission. Both alpha1 and beta-adrenoceptors are involved in this antagonistic action.

Key words

Apomorphine Hypothermia Noradrenaline uptake inhibitors 5-Hydroxytryptamine uptake inhibitors Antidepressant drugs Alpha1-adrenoceptors Beta-adrenoceptors 5-Hydroxytryptamine receptors Mice 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Amin MM, Ananth JV, Coleman BS, Darcourt G, Farkas T, Goldstein B, Lapierre YD, Paykel E, Wakelin JS (1984) Fluvoxamine: antidepressant effects confirmed in a placebo-controlled international study. Clin Neuropharmacol 7, suppl 1: S 317Google Scholar
  2. Barnett A, Goldstein J, Taber RI (1972) Apomorphine-induced hypothermia in mice: a possible dopaminergic effect. Arch Intern Pharmacodyn Ther 198:242–247Google Scholar
  3. Cohn JB (1983) Fluoxetine hydrochloride in the treatment of major depressive disorder. Abstracts of the 7th World Congress of Psychiatry, Vienna (Austria), 11–16 July 1983, p 393, abstract F 662Google Scholar
  4. Colpaert FC, Van Bever WFM, Leysen JEMF (1976) Apomorphine: chemistry, pharmacology and biochemistry. Internat Rev Neurobiol 19:225–268Google Scholar
  5. Cox B, Kerwin R, Lee TF (1978) Dopamine receptors in the central thermoregulatory pathways of the rat. J Physiol 282:471–483Google Scholar
  6. Cox B, Lee TF (1977) Do central dopamine receptors have a physiological role in brain function? Br J Pharmacol 61:83–86Google Scholar
  7. De Jonge A, Van Meel JCA, Timmermans PBMWM, Van Zwieten PA (1981) A lipophilic, selective α1-adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587). Life Sci 28:2009–2016Google Scholar
  8. Delini-Stula A, Hauser K, Baumann P, Olpe H-R, Waldmeier P, Storni A (1982) Stereospecificity of behavioural and biochemical responses to oxaprotiline — a new antidepressant. Adv Biochem Psychopharmacol 31:265–275Google Scholar
  9. Di Chiara G, Gessa GL (1978) Pharmacology and neurochemistry of apomorphine. Adv Pharmacol Chemother 15:87–160Google Scholar
  10. Feighner JP, Roffman M (1981) An early clinical trial of oxaprotiline in hospitalized patients with primary depression. Curr Ther Res 29:363–369Google Scholar
  11. Feldmann HS, Denber HCB (1982) Longterm study of fluvoxamine. A new rapid acting antidepressant. Int Pharmacopsychiatr 17:114–122Google Scholar
  12. Frances H, Puech AJ, Chermat R, Simon P (1979) Are psychopharmacological effects of beta-adrenergic stimulants central or peripheral? Pharmacol Res Commun 11:273–278Google Scholar
  13. Frances H, Puech AJ, Danti S, Simon P (1983) Attempt at pharmacological differentiation of central β-adrenergic receptors. Eur J Pharmacol 92:223–230Google Scholar
  14. Fuxe K, Sjöqvist F (1972) Hypothermic effect of apomorphine in the mouse. J Pharm Pharmacol 24:702–705Google Scholar
  15. Gottlieb P, Wandall T, Fredricson Overø K (1980) Initial, clinical trial of a new, specific 5-HT reuptake inhibitor, citalopram (Lu 10-171). Acta Psychiatr Scand 62:236–244Google Scholar
  16. Hall H, Ögren S-O (1981) Effects of antidepressant drugs on different receptors in the brain. Eur J Pharmacol 70:393–407Google Scholar
  17. Hyttel J (1982) Citalopram — pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuro-Psychopharmacol Biol Psychiatr 6:277–295Google Scholar
  18. Itil TM, Shrivastava RK, Mukherjee S, Coleman B, Michael ST (1983) A double blind placebo-controlled study of fluvoxamine and imipramine in outpatients with primary depression. Br J Clin Pharmacol 15:433–438Google Scholar
  19. Kobinger W, Pichler L (1983) Subgroups of α-adrenoceptors: selectivity of drugs and receptor importance in various target systems. In: Bock KD (ed) Catapresan (Clonidin) Wege der Entwicklung eines Pharmakons, Editio Cantor, D-7960 Aulendorf 1983, pp 83–91Google Scholar
  20. Kragh-Sørensen P (1983) A controlled, double-blind multicentre trial comparing clomipramine and a new, highly selective 5-HT uptake inhibitor, citalopram (Lu 10-171). Abstracts of the 7th World Congress of Psychiatry, Vienna (Austria), 11–16 July 1983, p 482, abstract P 179Google Scholar
  21. Kulkarni SK (1980) Apomorphine hypothermia: Interaction with serotonergic agents. Pol J Pharmacol Pharm 32:15–20Google Scholar
  22. Lecrubier Y, Puech AJ, Jouvent R, Simon P, Widlöcher D (1980) A beta-adrenergic stimulant salbutamol vs clomipramine in depression: a controlled study. Br J Psychiatry 136:354–358Google Scholar
  23. Lee EHY, Geyer MA (1984) Indirect effects of apomorphine on serotoninergic neurons in rats. Neuroscience 11:437–442Google Scholar
  24. Lindegaard Pedersen O, Kragh-Sørensen P, Bjerre M, Fredricson Overø K, Gram LF (1982) Citalopram, a selective serotonin reuptake inhibitor: clinical antidepressive and long term effect — A phase II study. Psychopharmacology 77:199–204Google Scholar
  25. Loque J, Sachais B, Feighner JP (1979) Comparisons of maprotiline with imipramine in severe depression: A multicenter controlled trial. J Clin Pharmacol 19:64–74Google Scholar
  26. Maj J, Palider W, Rawłów A (1979) Trazodone, a central serotonin antagonist and agonist. J Neural Transm 44:237–248Google Scholar
  27. Maj J, Pawłowski L, Wiszniowska G (1974) The effect of tricyclic antidepressants on apomorphine-induced hypothermia in the mouse. Pol J Pharmacol Pharm 26:329–336Google Scholar
  28. Menon MK, Vivonia CA (1981) Modification of apomorphine hypothermia by drugs affecting brain 5-hydroxytryptamine function. Eur J Pharmacol 76:223–227Google Scholar
  29. Menon MK, Vivonia CA, Kling AS (1984) Pharmacological studies on the antagonism by antidepressants of the hypothermia induced by apomorphine. Neuropharmacology 23:121–127Google Scholar
  30. Mertens C (1983) A controlled double-blind clinical tral with a new highly selective 5-HT-re-uptake inhibitor, citalopram (Lu 10-171) versus mianserin in depressed patients. Abstracts of the 7th World Congress of Psychiatry, Vienna (Austria), 11–16 July 1983, p 441, abstract F 924Google Scholar
  31. Puech AJ, Chermat R, Poncelet M, Doare L, Simon P (1981) Antagonism of hypothermia and behavioral response to apomorphine: a simple, rapid and discriminating test for screening antidepressants and neuroleptics. Psychopharmacology 75:84–91Google Scholar
  32. Roffman M, Gould EE, Brewer SJ et al. (1982) A double-blind comparative study of oxaprotiline with amitriptyline and placebo in moderate depression. Curr Ther Res 32:247–256Google Scholar
  33. Rokosz-Pelc A, Antkiewicz-Michaluk L, Vetulani J (1980) 5-Hydroxytryptamine-like properties onm-chlorophenylpiperazine: comparison with quipazine. J Pharm Pharmacol 32:220–222Google Scholar
  34. 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-Schmiedeberg's Arch Pharmacol 308:159–163Google Scholar
  35. Schelkunov EL (1968) Apomorphine hypothermia in mice as the test for differentiation of antidepressants and cholinolytics. In: Experimental studies of antidepressants (Proc. of Bechterev Psychoneurological Inst., vol 45), Lapin IP, ed, Leningrad 1968, pp 62–77Google Scholar
  36. Schelkunov EL (1977) Efficacy of neuroleptics and antidepressants in the test of apomorphine hypothermia and some data concerning neurochemical mechanism of the test. Psychopharmacology 55:87–95Google Scholar
  37. Simon P, Lecrubier Y, Jouvent R, Puech AJ, Allilaire JF, Widlöcher D (1978) Experimental and clinical evidence of the antidepressant effect of a beta-adrenergic stimulant. Psychol Med 8:335–338Google Scholar
  38. Souto M, Frances H, Lecrubier Y, Puech AJ, Simon P (1979) Antagonism byd,l-propranolol of imipramine effects in mice. Eur J Pharmacol 60:105–108Google Scholar
  39. Strömgren LS, Friderichsen T (1971) Lu 5-003 i antidepressiv terapi. Nord Psykiat Tidskr 25:119–128Google Scholar
  40. Vaatstra WJ, Deiman-Van Aalst WMA, Eigeman L (1981) DU 24565, a quipazine derivative, a potent selective serotonin uptake inhibitor. Eur J Pharmacol 70:195–202Google Scholar
  41. Wright JH, Denber HCB (1978) Clinical trial of fluvoxamine: a new serotonergic antidepressant. Curr Ther Res 23:83–89Google Scholar
  42. Øfsti E (1982) Citalopram — a specific 5-HT-reuptake inhibitor — as an antidepressant drug: A phase II multicentre trial. Prog Neuro-Psychopharmacol Biol Psychiatr 6:327–335Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • L. Pawłowski
    • 1
  • H. Mazela
    • 1
  1. 1.Institute of PharmacologyPolish Academy of SciencesKrakówPoland

Personalised recommendations