Skip to main content
SpringerLink
Log in

Study of the clomipramine-morphine interaction in the forced swimming test in mice

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

Abstract

Tricyclic antidepressant-morphine interactions have been extensively studied on pain tests but less often on tests predictive of antidepressant activity. The effects of clomipramine (CMI) and morphine were tested on the forced swimming test in mice after pretreatment with CMI, morphine or saline. Like CMI, though less so, morphine was significantly active. Morphine pretreatment partially inhibited the effect of CMI irrespective of the morphine pretreatment dose, but reduction of morphine activity by CMI was non-significant. Acquired tolerance to morphine occurred, but not to CMI. The mechanisms at work were discussed. CMI and desmethylclomipramine (DCMI) plasma levels remained the same after morphine pretreatment, ruling out a pharmacokinetic mechanism. The interaction implied involvement of opiate systems. CMI might have been acting on two different opiate receptor populations, one sensitive to morphine pretreatment, the other not. The mechanism of this action seems to be different from that of morphine.

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

  • Agren H, Terenius L (1985) Hallucinations in patients with major depression, interactions between CSF monoaminergic and endorphinergic indices. Affect Dis 9:25–34

    Google Scholar 

  • Almay BGL, Johansson F, Von Knorring L, Sedvall G, Terenius L (1980) Relationships between C.S.F. levels of endorphins and monoamines metabolites in chronic pain-patients. Psychopharmacology 67:139–142

    Google Scholar 

  • Angst J, Autenrieth V, Brem F, Kovkkov M, Meyer H, Stassen HH, Storck U (1979) Use of narcotic antagonists to study the role of endorphins in normal and psychiatric patients. In: Usdin E, Bunney WE, Kline NS (eds). Endorphins in mental health research. MacMillan, New York, pp 518–528

    Google Scholar 

  • Antkiewicz-Michaluk L, Rokosz-Pelc A, Vetulani J (1984) Increase in rat cortical (3H) naloxone binding site density after chronic administration of antidepressant agents. Eur J Pharmacol 102:179–181

    Google Scholar 

  • Axelrod J (1956) The enzymatic N-demethylation of narcotic drugs. J Pharmacol Exp Ther 117:322–330

    Google Scholar 

  • Baraldi M, Poggioli R, Santi M, Vergoni AV, Bertoli A (1983) Antidepressants and opiates interactions: pharmacological and biochemical evidences. Pharmacol Res Commun 15:843–857

    Google Scholar 

  • Biegon A, Samuel D (1980) Interaction of tricyclic antidepressants with opiate receptors. Biochem Pharmacol 29:460–462

    Google Scholar 

  • Botney M, Fields HL (1983) Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system. Ann Neurol 13:160–164

    Google Scholar 

  • Chesher GB, Chan B (1977) Footshock induced analgesia in mice: its reversal by naloxone and cross tolerance with morphine. Life Sci 21:1569–1574

    Google Scholar 

  • Davis GC, Buchsbaum MS, Bunney WE Jr (1981) Opiates, opioid peptides and psychiatry. Ann NY Acad Sci 362:67–75

    Google Scholar 

  • De Felipe MDC, De Ceballos ML, Gil C, Fuentes JA (1985) Chronic antidepressant treatment increases enkephalin levels in n. accumbens and striatum of the rat. Eur J Pharmacol 112:119–122

    Google Scholar 

  • Delander GE, Porthoghese PS, Takemori AE (1984) Role of spinal mu opioid receptors in the development of morphine tolerance and dependance. J Pharmacol Exp Ther 231:91–96

    Google Scholar 

  • Devoize JL, Rigal F, Eschalier A, Trolèse JF (1982) Naloxone inhibits clomipramine in mouse forced-swimming test. Eur J Pharmacol 78:229–231

    Google Scholar 

  • Devoize JL, Rigal F, Eschalier A, Trolèse JF, Renoux M (1984) Influence of naloxone on antidepressant drug effects in the forced-swimming test in mice. Psychopharmacology 84:71–75

    Google Scholar 

  • Eschalier A, Montastruc JL, Devoize JL, Rigal F, Gaillard-Plaza G, Pechadre JC (1981) Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats. Eur J Pharmacol 74:1–7

    Google Scholar 

  • Eschalier A, Rigal F, Devoize JL, Trolèse JF, Grillon C (1983) Morphine pretreatment reduces clomipramine effect in mouse forced-swimming test. Eur J Pharmacol 91:505–507

    Google Scholar 

  • Fialip J, Makambila MC, Rigal F, Devoize JL, Varoquaux O, Eschalier A (1986) Chronic administration of clomipramine inhibits morphine hot plate analgesia. Life Sci 38:1097–1103

    Google Scholar 

  • Godefroy F, Weil-Fugazza J, Bineau-Thurotte M, Besson JM (1981) The relationship between morphine analgesia and the activity of bulbo-spinal serotonergic system as studied by tolerance phenomenon. Brain Res 226:201–210

    Google Scholar 

  • Godefroy F, Butler SH, Weil-Fugazza J, Besson JM (1986) Do acute or chronic tricyclic antidepressants modify morphine antinociception in arthritic rats? Pain 25:233–244

    Google Scholar 

  • Goldstein A (1979) Enkephalin and pain: a critical review. In: Beers RF, Bassett EG (eds), Mechanisms of pain and analgesic compounds. Raven, New York, pp 249–262

    Google Scholar 

  • Goldstein FJ, Mojaverian P, Ossipov MH, Swanson BN (1982) Elevation in analgetic effect and plasma levels of morphine by desipramine in rats. Pain 14:279–282

    Google Scholar 

  • Gram LF (1977) Factors influencing the metabolism of tricyclic antidepressants. Dan Med Bull 24:81–89

    Google Scholar 

  • Gunne LM, Lindstrom L, Widerlov E (1979) Possible role of endorphins in schizophrenia and other psychiatric disorders. In: Usdin E, Bunney WE Jr, Kline NS (eds) Endorphins in mental health research, pp 547–552

  • Isenberg K, Cicero TJ (1984) Possible involvement of opiate receptors in the pharmacological profiles of antidepressant compounds. Eur J Pharmacol 103:57–63

    Google Scholar 

  • Janowsky D, Judd L, Huey L, Roitman N, Parker D, Segal D (1978) Naloxone effects on manic symptoms and growth-hormone levels. Lancet II:320–321

    Google Scholar 

  • Kastin AJ, Scollan EL, Ehrensing RH, Schally AV, Coy DH (1978) Enkephalin and other peptides reduce passiveness. Pharmacol Biochem Behav 9:515–519

    Google Scholar 

  • Kellstein DF, Malseed RT, Goldstein FJ (1984) Contrasting effects of acute vs chronic tricyclic antidepressant treatment on central morphine analgesia. Pain 20:323–334

    Google Scholar 

  • Levine JD, Gordon NC, Smith R, McBryde R (1986) Desipramine enhances opiate-postoperative analgesia. Pain 27:45–49

    Google Scholar 

  • Liu SJ, Wang RIH (1975) Increased analgesia and alterations in distribution and metabolism of methadone by desipramine in the rat. J Pharmacol Exp Ther 195:94–104

    Google Scholar 

  • Mackay AVP (1981) Endorphins and the psychiatrist. Trends Neurosci 4:9–11

    Google Scholar 

  • Malseed RT, Goldstein FJ (1979) Enhancement of morphine analgesia by tricyclic antidepressants. Neuropharmacology 18:827–829

    Google Scholar 

  • Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine- and nalorphin-like drugs in the nondependent and morphine dependent chronic spinal dog. J Pharmacol Exp Ther 197:517–532

    Google Scholar 

  • Neil A (1985) Affinities of some common opioid analgesics towards four binding sites in the mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 328:24–32

    Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    Google Scholar 

  • Reichenberg K, Gaillard-Plaza G, Montastruc JL (1985) Influence of naloxone on the antinociceptive effects of some antidepressant drugs. Arch Int Pharmacodyn Ther 275:78–85

    Google Scholar 

  • Reisine T, Soubrie P (1982) Loss of rat cerebral cortical opiate receptors following chronic desimipramine treatment. Eur J Pharmacol 77:39–44

    Google Scholar 

  • Somoza E, Galindo A, Bazan E, Guillamon A, Valencia A, Fuentes JA (1981) Antidepressants inhibit enkephalin binding to synaptosome-enriched fractions of rat brain. Neuropsychobiology 7:297–301

    Google Scholar 

  • Stengaard-Pedersen K, Schou M (1985) Opioid peptides and receptors in relation to affective illness. Effects of desipramine and lithium on opioid receptors in rat brain. Acta Pharmacol Toxicol 56:170–179

    Google Scholar 

  • Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology 85:367–370

    Google Scholar 

  • Taiwo YO, Fabian A, Pazoles CJ, Fields HL (1985) Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord. Pain 21:329–337

    Google Scholar 

  • Terenius L, Wahstrom A, Lindstrom L, Widerlov E (1976) Increased C.S.F. levels of endorphines in chronic psychosis. Neurosci Lett 3:157–162

    Google Scholar 

  • Walsh TD (1983) Antidepressants in chronic pain. Clin Neuropharmacol 6:271–295

    Google Scholar 

  • Woolfe G, MacDonald AD (1944) Evaluation of the analgesic action of pethidine-hydrochloride. J Pharmacol Exp Ther 80:300–307

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Pharmacologie, INSERM U195, Faculté de Médecine, 28 place Henri Dunant, F-63001, Clermont-Ferrand Cédex, France

    A. Eschalier & M.-C. Makambila

  2. Laboratoire de Chimie Biologique et Pharmacodynamie, Faculté de Pharmacie, F-63001, Clermont-Ferrand Cédex, France

    J. Fialip

  3. Laboratoire de Pharmacologie, Faculté de Médecine Paris-Ouest, 15 rue de l'Ecole de Médecine, F-75270, PARIS Cédex 06, France

    O. Varoquaux

Authors
  1. A. Eschalier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Fialip
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Varoquaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M.-C. Makambila
    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

Eschalier, A., Fialip, J., Varoquaux, O. et al. Study of the clomipramine-morphine interaction in the forced swimming test in mice. Psychopharmacology 93, 515–519 (1987). https://doi.org/10.1007/BF00207245

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00207245

Key words

Search

Navigation