Advertisement
Original article| Volume 34, ISSUE 1-2, P100-107, July 01, 1993

Download started.

Ok

Effect of mixed (RB 38A) and selective (RB 38B) inhibitors of enkephalin degrading enzymes on a model of depression in the rat

DOI:https://doi.org/10.1016/0006-3223(93)90262-C
Effect of mixed (RB 38A) and selective (RB 38B) inhibitors of enkephalin degrading enzymes on a model of depression in the rat
Previous ArticleEffects of alcohol on the EEG in Asian men with genetic variations of ALDH2
Next ArticleState specificity of DST abnormalities in geriatric depression
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      This is a study of the effects of the endogenous opioid peptides, enkephalins, on learned helplessness, an experimental model of depression in rats. For this purpose, the responses induced by RB 38A, a mixed inhibitor of enkephalin catabolism, and RB 38B, a selective inhibitor of neutral endopeptidase EC 3.4.24.11, were compared with the antidepressive effect induced by imipramine, RB 38A and RB 38B induced an imipramine-like effect in reducing helpless behavior, as illustrated by the decrease in the number of escape failures. According to the different pharmacological potential of both inhibitors to reduce enkephalin metabolism, complete inhibition of enkephalins (RB 38A) produced a higher response than that obtained with a partial inhibitor (RB 38B). On the other hand, naloxone (NLX) was found to facilitate the induction of learned helplessness, and to antagonize the effect of both enkephalin-degrading enzyme inhibitors. These results suggest that modifications in the activity of the endogenous opioid system could take place in this model of depression. The antidepressant-like effects induced by RB 38B, and especially by RB 38A, in the learned helplessness paradigm suggest that new mixed enkephalinase inhibitors, able to cross the blood-brain barrier, could provide a new strategy in the treatment of affective disorders.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Agrën H.
        • Terenius L.
        • Wahlström A.
        Depressive phenomenology and levels of cerebrospinal fluid endorphins.
        Ann NY Acad Sci. 1982; 398: 388-398
        • Angst J.
        • Autenrieth V.
        • Brem F.
        • et al.
        Preliminary results of treatment with beta-endorphin in depression.
        in: Usdin E. Bunney Jr., W.E. Kline N.S. Endorphins in Mental Health Research. McMillan, London1979: 518-528
        • Ben Natan L.
        • Chaillet P.
        • Lecomte J.M.
        • Marcais H.
        • Uchida G.
        • Costentin J.
        Involvement of endogenous enkephalins in the mouse “behavioral despair” test.
        Eur J Pharmacol. 1984; 97: 304-310
        • Crowley T.J.
        • Wagner J.E.
        • Zerbe G.
        • McDonald M.
        Naltrexone-induced dysphoria in former opioid addicts.
        Am J Psychiatry. 1985; 142: 1081-1084
        • DeWitte P.H.
        • Heideberg C.
        • Roques P.B.
        Kelatorphan, a potent enkephalinase inhibitor, and opioid receptor agonist DAGO and DTLET, differentially modulate self-stimulation behavior depending on the site of administration.
        Neuropharmacology. 1989; 28: 667-676
        • Emrich H.M.
        A possible role of opioids substances in depression.
        in: Typical and Atypical Antidepressants. Vol. 1: Clinical Practice. Raven Press, New York1981: 77-84
        • Eschalier A.
        • Montastruc J.L.
        • Decoize J.L.
        • Rigal F.
        • Gaillard-Plaza G.
        • Pechadre J.C.
        Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats.
        Eur J Pharmacol. 1981; 74: 1
        • Fink M.
        • Simeon J.
        • Itil T.M.
        • Freedam H.
        Clinical antidepressant activity of cyclazocine, a narcotic antagonist.
        Clin Pharmacol Ther. 1970; 11: 41-43
        • Fournié-Zaluski M.C.
        • Coric P.
        • Turcaud S.
        • et al.
        “Mixed inhibitor-prodrug” as a new approach towards systematically active inhibitors of enkephalin-degrading enzymes.
        J Med Chem. 1992; 34: 2473-2481
        • Gold M.S.
        • Pottash A.C.
        • Sweeney D.
        • Martin D.
        • Extein I.
        Antimanic, antidepressant, and antipanic effects of opiates: Clinical, neuroanatomical, and biochemical evidence.
        Ann NY Acad Sci. 1982; 398: 140-150
        • Hamon M.
        • Gozlan H.
        • Bourgoin S.
        • et al.
        Opioid receptors and neuropeptides in the CNS in rats treated chronically with amoxapine or amitriptilline.
        Neuropharmacology. 1987; 26: 531-539
        • Inturrisi C.E.
        • Alexopoulos G.
        • Lipman R.
        • Foley K.
        • Rossier J.
        Beta-endorphin immunoreactivity in the plasma of psychiatric patients receiving electroconvulsive treatment.
        Ann NY Acad Sci. 1982; 398: 413-422
        • Lecomte J.M.
        • Costentin J.
        • Vlaiculescu A.
        • et al.
        Pharmacological properties of acetorphan, a parenterally active “enkephalinase” inhibitor.
        J Pharmacol Exp Ther. 1986; 237: 937-944
        • Maldonado R.
        • Daugé J.
        • Feger J.
        • Roques B.P.
        Chronic blockade of D2 but not D1 dopamine receptors facilitates behavioral responses to endogenous enkephalins, protected by kelatorphan, administered in the accumbens in rats.
        Neuropharmacology. 1990; 29: 215-223
        • Maldonado R.
        • Feger J.
        • Fournié-Zaluski M.C.
        • Roques B.P.
        Differences in physical dependence induced by selective mu or delta opioid agonists and by endogenous enkephalins protected by peptidases inhibitors.
        Brain Res. 1990; 520: 247-254
        • Malfroy B.
        • Swert J.P.
        • Guyon A.
        • Roques B.P.
        • Schwartz J.C.
        High-affinity enkephalin-degrading peptidase in brain is increased after morphine.
        Nature. 1978; 276: 523-526
        • Martin P.
        • Soubrié P.
        • Simon P.
        Noradrenergic and opioid mediation of tricyclic-induced reversal of escape deficits caused by inescapable shock pretreatment in rats.
        Psychopharmacology. 1986; 90: 90-94
        • Martin P.
        • Soubrié P.
        • Simon P.
        The effects of monoamine oxidase inhibitors compared with classical tricyclic antidepressants on learned helplessness paradigm.
        Prog Neuro Psychopharmacol Biol Psychiatry. 1987; 11: 1-7
        • Massol J.
        • Martin P.
        • Soubrié P.
        • Simon P.
        Triiodothyroacetic-acid-induced reversal of learned helplessness in rats.
        Eur J Pharmacol. 1987; 134: 345-348
        • Meucci E.
        • Delay-Goyet P.
        • Roques B.P.
        • Zajac J.M.
        Binding in vivo of selective mu and delta opioid receptor agonists.
        Eur J Pharmacol. 1989; 171: 167-178
        • Missagh A.
        • Gianoulakis Ch.
        • Vasavan N.P.
        The effect of electroconvulsive therapy on endorphins in depression.
        Biol Psychiatry. 1988; 23: 459-464
        • Nabeshima T.
        • Katoh A.
        • Kameyama T.
        Inhibition of enkephalin degradation attenuated stress-induced motor suppression (Conditioned Suppression of Motility).
        J Pharmacol Exp Ther. 1988; 244: 303-309
        • Noble F.
        • Soleilhac J.M.
        • Lucas-Soroca E.
        • Turcaud S.
        • Fournié-Zaluski M.C.
        • Roques B.P.
        The first systematicly active mixed inhibitor of enkephalin degrading enzymes RB 101 induces potent analgesic responses in mice and rats.
        J Pharmacol Exp Ther. 1992; 261: 181-190
        • Noble F.
        • Coric P.
        • Fournié-Zaluski M.C.
        • Roques B.P.
        Lack of physical dependence in mice after repeated systemic administration of the mixed inhibitor prodrug of enkephalin-degrading enzymes, RB 101.
        Eur J Pharmacol. 1992; 223: 91-96
        • Pellegrino L.J.
        • Pellegrino A.S.
        • Cushman A.J.
        A Stereotaxic Atlas of the Rat Brain.
        Plenum Press, New York and London1979
        • Pollard H.
        • de la Blume S.
        • Bouthenet M.L.
        • Schwartz J.C.
        • Ronco P.
        • Verroust P.
        Characterization of two probes for the localization of enkephalinase in rat brain [3H]thiorphan and 125l-labeled monoclonal antibody.
        Eur J Pharmacol. 1987; 133: 155-164
        • Roques B.P.
        • Fournié-Zaluski
        • Soroca E.
        • et al.
        The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice.
        Nature. 1980; 288: 286-288
        • Roques B.P.
        • Fournié-Zaluski M.C.
        Enkephalin degrading enzyme inhibitors: A physiological way to new analgesic and psychoactive agents.
        in: Opioid Peptides: Molecular Pharmacology, Biosynthesis and Analysis. NIDA Research Monograph Series. 1986: 128-154 (Bethesda, MD)
        • Roques B.P.
        • Dauge V.
        • Gacel G.
        • Fournié-Zaluski M.C.
        Selective agonists and antagonists of delta opioid receptors and inhibitors of enkephalins metabolism. Potential use in treatment of mental illness.
        in: Shagass C. Jossiasen R.C. Bridger W.H. Weiss K.J. Stoff D. Simpson G.M. Biological Psychiatry 1985 Developments in Psychiatry. Elsevier, New York1986: 287-289
        • Schmauss C.
        • Emrich H.M.
        Narcotic antagonist and opioid treatment in psychiatry.
        in: Rogers R.J. Cooper S.J. Endorphins, Opiates and Behavioral Processes. Wiley, New Delhi1988: 327-351
        • Schmidt C.
        • Peyroux J.
        • Noble F.
        • Fournié-Zaluski M.C.
        • Roques B.P.
        Analgesic responses elicited by endogenous enkephalins (protected by mixed peptidase inhibitors) on a variety of morphine-sensitive noxious tests.
        Eur J Pharmacol. 1991; 192: 253-262
        • Seligman M.E.P.
        • Rossellini R.A.
        • Kozak M.
        Learned Helplessness in the rat: reversibility, time course and immunization.
        J Comp Physiol Psychol. 1975; 88: 542-547
        • Trampus M.
        • Ongini E.
        • Varani K.
        • Borea A.
        The neutral endopeptidase 24.11 inhibitor SCH 34826 does not change opioid binding but reduces D1 dopamine receptors in the rat brain.
        Eur J Pharmacol. 1991; 194: 17-23
        • Turner A.J.
        • Matsas R.
        • Kenny A.J.
        Endopeptidase 24.11 and neuropeptide metabolism.
        Biochem Soc Trans. 1985; 13: 39-42
        • Waksman G.
        • Bouboutou R.
        • Devin J.
        • Besselièvre R.
        • Fournié-Zaluski M.C.
        • Roques B.P.
        Binding of the bidentate inhibitor [3H]HACBO-Gly to the rat brain neutral endopeptidase “enkephalinase”.
        Biochem Biophys Res Commun. 1985; 131: 262-268
        • Willner P.
        The validity of animal models of depression.
        Psychopharmacology. 1984; 83: 1-16
        • Willner P.
        Animal models of depression: An overview.
        Pharmacol Ther. 1990; 45: 425-455
        • Xie J.
        • Soleihac J.
        • Schmidt C.
        • Peuroux J.
        • Roques B.P.
        • Fournié-Zaluski M.C.
        New kelatorphan-related inhibitors of enkephalin metabolism: improved antinociceptive properties.
        J Med Chem. 1989; 32: 1497-1503

      Article info

      Publication history

      Received in revised form: March 17, 1993
      Received: February 28, 1992

      Footnotes

      ☆This work was partly supported by DGICYT grant number PN89-0166 and Acción Integrada Hispano-Francesa number 229-03 and 313-A.

      Identification

      DOI: https://doi.org/10.1016/0006-3223(93)90262-C

      Copyright

      © 1993 Published by Elsevier Inc.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX