Summary
The present study was designed to find out whether the prolonged administration of imipramine (IMI) or electroconvulsive shock (ECS) influences levels of endogenous enkephalins in the nucleus accumbens (NAS) and the ventral tegmentum (VTA) of the rat. Ressults indicate that treatment with IMI as well as with ECS has a profound effect on the levels of enkephalins in both structures. In the NAS both treatments lead to an increase in the levels of endogenous enkephalins and this effect is accompanied by an increase in mRNA coding for proenkephalin (measured by in situ hybridization) in this structure, indicating the enhancement of biosynthesis of endogenous enkephalinergic peptides following antidepressant treatment. The results are discussed in the light of the hypothesis concerning the influence of endogenous enkephalins on mesolimbic dopamine neurons, the activity of which plays a crucial role in the etiology of depression.
Similar content being viewed by others
References
Bannon MJ, Deutch AY, Tam S-Y, Zamir N, Eskay RL, Lee JM, Maggio JE, Roth RH (1986) Mild foot shock stress dissociates substance P from substance K and dynorphin from Met- and Leu-enkephalin. Brain Res 381: 393–396
Cooper SJ (1991) Interactions between endogenous opioids and dopamine: implications for reward and awersion. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopamine system: from motivation to action. Wiley, Chichester, pp 331–366
De Ceballos ML, Jenner P, Marsden CD (1986) Acute and repeated administration of sulpiride alters Met- and Leu-enkephalin content of rat brain. Neurosci Lett 68: 322–326
Goldstein A (1976) Opioid peptides (endorphins) in pituitary and brain. Science 193: 1081–1086
Hakan RL, Henrikson SJ (1989) Opiate influences on nucleus accumbens neuronal electrophysiology: dopamine and non-dopamine mechanisms. J Neurosci 9: 3538–3546
Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12: 483–488
Kalivas PW, Abhold R (1987) Enkephalin release into the ventral tegmental area in response to stress: modulation of mesocorticolimbic dopamine. Brain Res 414: 339–348
Klimek V, Maj J (1989) Repeated administration of antidepressants enhances agonist affinity for mesolimbic D-2 receptors. J Pharm Pharmacol 41: 555–558
Klimek V, Maj J (1990) The effect of antidepressant drugs given repeatedly on the binding of3H-SCH 23390 and3H-Spiperone to dopaminergic receptors. In: Gessa GL, Serra G (eds) Advances in the biosciences 77. Pergamon Press, Oxford, pp 159–166
Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ (1988) Anatomy of CNS opioid receptors. Trends Pharmacol Sci 11: 308–314
Musacchio JM (1990) The psychotomimetic effects of opiates and the sigma receptor. Neuropsychopharmacology 3: 191–200
Naber D (1988) Clinical relevance of endorphins in psychiatry. Prog Neuropsychopharmacol Biol Psychiatry 12: S119-S135
Naber D (1993) Opioids in etiology and treatment of psychiatric disorders. In: Herz A (ed) Opioids II. Springer, Berlin Heildelberg New York Tokyo, pp 781–801
Palkovits M, Brownstein MJ (1988) Maps and guide to microdissection of the rat brain. Elsevier, New York
Pentney RJW, Gratton A (1991) Effects of local delta and mu opioid receptor activation on basal and stimulated dopamine release in striatum and nucleus accumbens of rat: an in vivo electrochemical study. Neuroscience 45: 95–102
Pierzchała K, Houdi A, Van Loon GR (1987) Nicotine-induced alterations in brain regional concentrations of native and cryptic Met- and Leu-enkephalin. Peptides 8: 1035–1043
Rossetti ZL, Lai M, Hmaidan Y, Gessa GL (1993) Depletion of mesolimbic dopamine during behavioral despair: prtial reversal by chronic imipramine. Eur J Pharmacol 242: 313–315
Serra G, Forgione A, D'Aquila PS, Collu M, Fratta W, Gessa GL (1990) Possible mechanism of antidepressant effect of L-sulpiride. Clin Neuropharmacol 13 [Suppl 1]: S76-S85
Serra G, Collu M, D'Aquila PS, Gessa GL (1992) Role of the mesolimbic dopamine system in the mechanism of action of antidepressants. Pharmacol Toxicol 71 [Suppl 1]: 72–85
Spanagel R, Herz A, Shippenberg TS (1992) Opposing tonically active endogenous opioid systems modulate the mesolimbic dopamine pathway. Proc Natl Acad Sci USA 89: 2046–2050
Willner P, Muscat R, Papp M (1992) Chronic mild stress induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 16: 525–534
Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40: 191–225
Young WS, Bonner TI, Braun MR (1986) Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. Proc Natl Acad Sci USA 83: 9827–9831
Zamir N, Palkovits M, Weber E, Mezey E, Brownstein A (1984) A dynorphinergic pathway of Leu-enkephalin production in rat substantia nigra. Nature 307: 643–645
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dziedzicka-Wasylewska, M., Rogoż, R. The effect of prolonged treatment with imipramine and electroconvulsive shock on the levels of endogenous enkephalins in the nucleus accumbens and the ventral tegmentum of the rat. J. Neural Transmission 102, 221–228 (1995). https://doi.org/10.1007/BF01281156
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01281156