Summary
The acute treatment of rats with diazepam induces pronounced changes in brain enkephalin concentrations, as was estimated for methionine(met)-enkephalin and in some representative experiments for leucine(leu)-enkephalin, employing highly specific radioimmunoassays. Diazepam selectively increased the enkephalin concentrations in the hypothalamus by about 35%, and lowered it in the corpus striatum by roughly 25%; no changes could be detected in the medulla oblongata/pons or midbrain. The drug-induced changes displayed a rapid onset. Peak effects were reached by 2 to 5 min after injection. Changes observed in the hypothalamus were only short lasting and were apparently paralleled by diazepam concentrations in the brain, whereas the decrease in the striatum was of markedly longer duration. Presently, the mechanism underlying all these changes in unknown. Whereas an increase in enkephalin concentrations in the hypothalamus may be discussed in terms of the anti-stress effect of benzodiazepines, the observed drop in striatal enkephalin is not obviously to be correlated to behavioural changes induced by these drugs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Billingsley, M. L., Kubena, R. K.: Effects of naloxone and picrotoxin on the sedative and anticonflict effects of benzodiazepines. Life Sci. 22, 897–906 (1978)
Braestrup, C., Squires, R. E.: Specific benzodiazepine receptors in rat brain characterized by high affinity 3H-diazepam binding. Proc. Natl. Acad. Sci. USA 74, 3805–3809 (1977)
Consolo, S., Garattini, S., Cadinsky, H.: Action of the benzodiazepines on the cholinergic system. In: Mechanism of action of benzodiazepines (E. Costa, P. Greengard, eds.), pp. 63–77. New York: Raven Press 1975
Corodi, H., Fuxe, K., Hökfelt, T.: The effect of some psychoactive drugs on central monoamine neurons. Eur. J. Pharmacol. 1, 363–368 (1967)
Costa, E., Fratta, W., Hong, J. S., Moroni, F., Yang, H.-Y. T.: Interactions between enkephalinergic and other neuronal systems. In: Advances in biochemical psychopharmacology, Vol. 18 (E. Costa, M. Trabucchi, eds.), pp. 217–226. New York: Raven Press 1978.
Duka, Th., Höllt, V., Przewłocki, R., Wesche, D.: Distribution of methionine- and leucine-enkephalin within the rat pituitary gland measured by highly specific radioimmunoassays. Biochem. Biophys. Res. Commun. 85, 1119–1127 (1978)
Duka, Th., Höllt, V., Herz, A.: In vivo receptor occupation by benzodiazepines and correlation with the pharmacological effect. Brain Res. (in press, 1979)
Elde, R., Hökfelt, T., Johansson, O., Terenius, L.: Immunohistochemical studies using antibodies to leu-enkephalin: initial observations on the nervous system of the rat. Neuroscience 1, 349–351 (1976)
Glowinski, J., Iversen, L.: Regional studies of catecholamines in the rat brain. I. Disposition of 3H-norepinephrine, 3H-dopamine and 3H-dopa in various brain regions of the brain. J. Neurochem. 13, 655–669 (1966)
Guidotti, A.: Synaptic mechanisms in the action of benzodiazepines. In: Psychopharmacology: a generation of progress (M. A. Lipton, A. Di Mascio, K. F. Killan, eds.), pp. 1349–1357. New York: Raven Press 1978.
Henderson, G., Hughes, J., Kosterlitz, H. W.: In vitro release of leuand met-enkephalin from the corpus striatum. Nature 271, 677–679 (1978)
Höllt, V., Przewłocki, R., Herz, A.: β-Endorphin-like immunoreactivity in plasma, pituitaries and hypothalamus of rats following treatment with opiates. Life Sci. 23, 1057–1066 (1978)
Iversen, L. L., Iversen, S. D., Bloom, F. E., Vargo, T., Guillemin, R.: Release of enkephalin from rat globus pallidus in vitro. Nature 271, 679–681 (1978)
Lorens, S. A., Sainati, S. M.: Naloxone blocks the excitatory effect of ethanol and chlordiazepoxide on lateral hypothalamic self stimulation behaviour. Life Sci. 23, 1359–1364 (1978)
Mao, C. C., Revuelta, A., Marco, E., Costa, E.: The turnover rate of GABA in brain nuclei of rats injected with DA receptor antagonists and GABA receptor agonists. In: Neuro-Psychopharmacology Vol. 2 (P. Deniker, C. Radouco-Thomas, A. Villeneuve, eds.), pp. 447–453. Oxford: Pergamon Press 1978
Möhler, H., Okada, T.: Benzodiazepine receptor demonstration in the central nervous system. Science 198, 849–851 (1977)
Moroni, F., Cheney, D. L., Peralta, E., Costa, E.: Opiate receptor agonists as modulators of γ-aminobutyric acid turnover in the nucleus caudatus, globus pallidus and substantia nigra of the rat. J. Pharmacol. Exp. Ther. 207, 870–877 (1978)
Osborne, H., Höllt, V., Herz, A.: Potassium-induced release of enkephalins from rat striatal slices. Eur. J. Pharmacol. 48, 219–221 (1978)
Pert, C. B., Bowie, D. L., Fong, B. T. W., Chang, J.-K.: Synthetic analogues of met-enkephalin which resist enzymatic destruction. In: opiates and endogenous opioid peptides (H. W. Kosterlitz, ed.), pp. 79–86. Amsterdam: Elsevier/North-Holland Biomedical Press 1976
Przewłocki, R., Höllt, V., Duka, Th., Kleber, G., Gramsch, Ch., Haarmann, I., Herz, A.: Long-term morphine treatment decreases endorphin levels in rat brain and pituitary. Brain Res. (in press, 1979)
Rommelspacher, H., Kuhar, M. J.: Effects of electrical stimulation on acetylcholine levels in central cholinergic nerve terminals. Brain Res 81, 243–251 (1974)
Rossier, J., Guillemin, R., Bloom, F.: Foot shock induced stress decreases leu5-enkephalin immunoreactivity in rat hypothalamus. Eur. J. Pharmacol. 48, 465–466 (1978)
Roth, R. H., Walters, J. T., Aghajanian, G. K.: Effect of impulse flow on the release and synthesis of dopamine in the rat striatum. In: Frontiers of catecholamine research (E. Usdin, S. H. Snyder, eds.), pp. 567–574. Oxford: Pergamon Press 1973
Schulz, R., Wüster, M., Simantov, R., Snyder, S. H., Herz, A.: Electrically stimulated release of opiate-like material from the myenteric plexus of the guinea-pig ileum. Eur. J. Pharmacol. 41, 347–348 (1977)
Simantov, R., Snyder, S. H.: Morphine-like peptides, leucine-enkephalin and methionine-enkephalin interaction with the opiate receptor. Mol. Pharmacol. 12, 987–998 (1976)
Stein, L., Wise, C. D., Beluzzi, J. D.: Effects of benzodiazepines on central serotonergic mechanisms. In: Mechanism of action of benzodiazepines (E. Costa, P. Greengard, eds.), pp. 29–44. New York: Raven Press 1975
Wang, R. Y., Aghajanian, G. K.: Antidromically identified serotonergic neurons in the rat midbrain raphe: Evidence for collateral inhibition. Brain Res. 132, 186–193 (1977)
Wesche, D., Höllt, V., Herz, A.: Radioimmunoassays of enkephalins. Regional distribution in rat brain after morphine treatment and hypophysectomy. Naunyn-Schmiedeberg's Arch. Pharmacol. 301, 79–82 (1977)
Whittaker, V. P., Barker, L. A.: The subcellular fractionation of brain tissue with special reference to the preparation of synaptosomes and their component organelles. In: Methods in neurochemistry, Vol. 2 (R. Fried, ed.), pp. 1–52. New York: Marcel Dekker, Inc., 1972
Wise, D. C., Stein, L.: Brain endorphin levels increase after long-term chlorpromazine treatment. In: Endorphins in mental health research (E. Usdin, W. Bunney, S. N. Kline, eds.), pp. 115–118. London: Macmillan Press 1978
Yang, H.-Y. T., Hong, J. S., Costa, E.: Regional distribution of leu-and met-enkephalin in rat brain. Neuropharmacology 16, 303–307 (1977)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Duka, T., Wüster, M. & Herz, A. Rapid changes in enkephalin levels in rat striatum and hypothalamus induced by diazepam. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 1–5 (1979). https://doi.org/10.1007/BF00498749
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498749