Skip to main content
SpringerLink
Log in

The significance ofβ-adrenoceptor down regulation in the desipramine action in the forced swimming test

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The present studies were undertaken to clarify whether centralβ-adrenoceptor down regulation is responsible for the greater effect of chronic treatment with desipramine (DMI) compared with acute treatment in the forced swimming test in rats. Repetitive administration of DMI activated the rat behaviour pattern and consequently reduced the duration of immobility. The degree of activation depended on the length of treatment, i.e. no effect when given in a single dose, moderate effect when given subchronically (3 doses) and marked activation after chronic (31 doses) treatment. Chronic treatment with DMI also produced a decrease in3H-dihydroalprenolol (3H-DHA) binding site in the cerebral cortex. Acute stimulation of brainβ-adrenoceptors by intracerebroventricular (i.c.v.) isoprenaline significantly, though partially, attenuated the behavioural effect of chronic DMI by β1-adrenoceptor-related mechanisms. Similarly, chronic i.c.v. co-administration of atenolol or practolol, β1-adrenoceptor antagonists, together with DMI attenuated bothβ-adrenoceptor down regulation and the behavioural activation by chronic DMI. On the other hand, chronic i.c.v administration of isoprenaline, supposedly leading to down regulation ofβ-adrenoceptors, facilitated the activating behavioural effect of DMI, as a single dose became effective. Changes, however, in3H-DHA binding parameters in the cerebral cortex were not observed after chronic isoprenaline. These results suggest that down regulation ofβ-adrenoceptors in brain is reponsible, at least in part, for the marked activatory effect of chronic DMI in the forced swimming test, possibly by reducing an inhibitory function of β1-adrenoceptor mediated mechanisms.

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

  • Asakura M, Tsukamoto T, Hasegawa K (1982) Modulation of rat brain α2- andβ-adrenergic receptor sensitivity following long-term treatment with antidepressants. Brain Res 235:192–197

    Google Scholar 

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

    Google Scholar 

  • Bergstrom DA, Kellar KJ (1979a) Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine. J Pharmacol Exp Ther 209:256–261

    Google Scholar 

  • Bergstrom DA, Kellar KJ (1979b) Effect of electroconvulsive shock on monoaminergic binding sites in rat brain. Nature 278:363–466

    Google Scholar 

  • Bylund DB, Snyder SH (1976) Beta-adrenergic receptor binding in membrane preparations from mammalian brain. Mol Pharmacol 12:568–580

    Google Scholar 

  • Clements-Jewery S (1978) The development of corticalβ-adrenoceptor subsensitivity in the rat by chronic treatment with trazodone, doxepin and mianserin. Neuropharmacology 17:779–781

    Google Scholar 

  • 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 neuronal adaptation. J Pharmacol Exp Ther 234:402–408

    Google Scholar 

  • Harden TK, Su YF, Perkins JP (1979) Catecholamine-induced desensitization involves an uncoupling ofβ-adrenergic receptors and adenylate cyclase. J Cycl Nucl Res 5:99–106

    Google Scholar 

  • Kitada Y, Miyauchi T, Satoh A, Satoh S (1981) Effects of antidepressants in the rat forced swimming test. Eur J Pharmacol 72:145–152

    Google Scholar 

  • Kitada Y, Miyauchi T, Kanazawa Y, Nakamichi H, Satoh S (1983a) Involvement of α- and β1-adrenergic mechanisms in the immobility-reducing action of desipramine in the forced swimming test. Neuropharmacology 22:1055–1060

    Google Scholar 

  • Kitada Y, Miyauchi T, Kosasa T, Satoh S (1983b) Further studies on the suppressing effect of isoproterenol on the immobility-reducing action of desipramine in the forced swimming test. Jpn J Pharmacol 33:867–873

    Google Scholar 

  • Kohno H, Sakurada T, Suzuki T, Kisara K, Satoh H (1981) Changes in ingestive behaviour, serum glucose and free fatty acids concentrations in rats following intracerebroventricular injection of spermine. Jpn J Pharmacol 31:863–873

    Google Scholar 

  • Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 192:256–275

    Google Scholar 

  • Minneman KP, Hegstrand LR, Molinoff PB (1978) The pharmacological specificity of beta-1 and beta-2 adrenergic receptors in rat heart and lung in vitro. Mol Pharmacol 16:21–33

    Google Scholar 

  • Minneman KP, Dibnear MD, Wolfe BB, Molinoff PB (1979) 35-1 and 35-2 receptors in rat cerebral cortex are independently regulated. Science 204:866–868

    Google Scholar 

  • Mishra R, Janowsky A, Sulser F (1980) Action of mianserin and zimelidine on the norepinephrine receptor coupled adenylate cyclase system in brain: Subsensitivity without reduction inβ-adrenergic receptor binding. Neuropharmacology 19:983–987

    Google Scholar 

  • Miyauchi T, Kitada Y, Satoh S (1981) Effects of acutely and chronically administered antidepressants on the brain regional 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the forced swimming rat. Life Sci 1921–1928

  • Miyauchi T, Kitada Y, Nakamichi H, Satoh S (1984)β-adrenoceptor mediated inhibition of behavioural action of desipramine and of central noradrenergic activity in forced swimming rats. Life Sci 35:543–551

    Google Scholar 

  • Oswald I, Brezinova, Dunleavy DLF (1972) On the slowness of action of tricyclic antidepressant drugs. Br J Psychiatr 120:673–677

    Google Scholar 

  • Peroutka SJ, Snyder SH (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science 210:88–90

    Google Scholar 

  • Platt JE, Stone EA (1982) Chronic restraint stress elicits a positive antidepressant response on the forced swim test. Eur J Pharmacol 82:179–181

    Google Scholar 

  • Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732

    Google Scholar 

  • Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: A new animal model sensitive to antidepressant treatment. Eur J Pharmacol 47:379–391

    Google Scholar 

  • Prange AJ Jr (1972) In discussion of Feighner JP, Kung LJ, Schuckit MA, Croughan J, and Broscoe W, Hormonal potentiation of imipramine and ECT in primary depression. Am J Psychiatr 128:1235–1254

    Google Scholar 

  • Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672

    Google Scholar 

  • Stone EA (1979) Subsensitivity to norepinephrine as a link between adaptation to stress and antidepressant theraphy: A hypothesis. Res Com Psychol Psychiat Behav 4:241–255

    Google Scholar 

  • Stone EA, Platt JE (1982) Brain adrenergic receptors and resistance to stress. Brain Res 237:405–414

    Google Scholar 

  • Sulser F, Vetulani J, Mobley P (1978) Mode of action of antidepressant drugs. Biochem Pharmacol 27:257–261

    Google Scholar 

  • Vetulani J, Sulser F (1975) Action of various antidepressant treatment reduces reactivity of noradrenergic cyclic AMP generating system in limbic forebrain. Nature 257:495–496

    Google Scholar 

  • Vetulani J, Stawarz RJ, Dingell JV, Sulser F (1976) A possible common mechanism of action of antidepressant treatments. Reduction in the sensitivity of the noradrenergic cyclic AMP generating system in the rat limbic forebrain. Naunyn-Schmiedeberg's Arch Pharmacol 293:109–114

    Google Scholar 

  • Vetulani J, Antkiewicz-Michaluk L, Rokosz-Pelc A, Pilc A (1983) Chronic electroconvulsive treatment enhances the density of [3H]prazosin binding sites in the central nervous system of the rat. Brain Res 275:392–395

    Google Scholar 

  • Vetulani J, Antkiewicz-Michaluk L, Rokosz-Pelc A (1984) Chronic administration of antidepressant drugs increased the density of cortical [3H]prazosin binding site in the rat. Brain Res 310:360–362

    Google Scholar 

  • Wang CH, U'Prichard DC (1980) Reciprocal alterations in rat brainβ- and α2-adrenergic receptor sites after chronic intracerebroventricular infusion of isoproterenol. Abstract of 10th Annual Meeting of Society for Neuroscience 5.3

  • Wolfe BB, Harden TK, Sporn JR, Molinoff PB (1978) Presynaptic modulation of beta-adrenergic receptors in rat cerebral cortex after treatment with antidepressant. J Pharmacol Exp Ther 207:446–457

    Google Scholar 

  • Zivin JA, Bartko JJ (1976) Statistics for disinterested scientists. Life Sci 18:15–26

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, 980, Sendai, Japan

    Yoshimi Kitada, Tatsuo Miyauchi, Takashi Kosasa & Susumu Satoh

Authors
  1. Yoshimi Kitada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatsuo Miyauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takashi Kosasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susumu Satoh
    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

Kitada, Y., Miyauchi, T., Kosasa, T. et al. The significance ofβ-adrenoceptor down regulation in the desipramine action in the forced swimming test. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 31–35 (1986). https://doi.org/10.1007/BF00569656

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00569656

Key words

Search

Navigation