Abstract
The aim of the present study was to investigate whether a disturbance of the central noradrenergic (NA) system could cause changes in gamma-aminobutyric acidB (GABAB) receptors in the rat frontal cortex. Manipulation of the NA projection to the frontal cortex was achieved by bilateral lesion of the locus coeruleus with 6-hydroxydopamine (6-OHDA) or chronic treatment with the NA reuptake blocker and antidepressant drug, desipramine. Precautions were taken to ensure that the GABAB receptor assay was performed optimally and was not confounded by the presence of endogenously generated GABA. The results show conclusively that manipulation of the NA projection did not result in any significant change in the number (Bmax) or affinity (Kd) of GABAB receptors in the frontal cortex. These results do not support the hypothesis that hypoactivity of the central NA system can lead to changes in cortical GABAB receptors and that antidepressant drugs act by increasing GABAB receptor binding in the frontal cortex.
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De Villiers, A. S., Russell, V. A., Carstens, M. E., Aalbers, C., Gagiano, C. A., Chalton, D. O., and Taljaard, J. J. F. 1986. Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in primary unipolar major depressive disorder. Psychiatry Res. 22:127–140.
Schildkraut, J. J. 1978. Current status of the catecholamine hypothesis of affective disorders. In Psychopharmacology: A generation of progress, pp 122–134, Lipton, MA, Dimascio, A., and Killam K. F. (Eds) New York, Raven Press.
Carstens, M. E., Engelbrecht, A. H., Russell V. A., Aalbers, C., Gagiano, C. A., Chalton, D. O., and Taljaard, J. J. F. 1986. Alpha2 adrenoceptor levels on platelets of patients with major depressive disorder. Psychiatry Res. 18:321–331.
Carstens, M. E., Engelbrecht, A. H., Russell, V. A., Van Zyl, A. M., and Taljaard, J. J. F. 1987. Biological markers in juvenile depression. Psychiatry Res. 23:77–88.
Siever, L. J., and Davis, K. L. 1984. Regulations of neurotransmitter systems: implications for the major psychiatric syndromes and their treatment. Psychopharmacol. Bull. 20:500–504.
Bunney, W. E. Jr., and Davis, J. M. 1965. Norepinephrine in depressive reactions: A review. Arch. Gen. Psychiat. 13:483–494.
Lloyd, K. G., Thuret, F., and Pilc, A. 1985. Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: A common action of repeated administration of different classes of antidepressant and electroshock. J. Pharmacol. Exp. Ther. 235:191–199.
Pilc, A., and Lloyd, K. G. 1984. Chronic antidepressants and GABA “B” receptors: A GABA hypothesis of antidepressant drug action. Life Sci. 35:2149–2154.
Suzdak, P. D., and Gianutsos, G. 1986. Effect of chronic imipramine or baclofen on GABA-B binding and cyclic AMP production in cerebral cortex. Eur. J. Pharmacol. 131:129–133.
Richelson, E., and Pfenning, M. 1984. Blockade by antidepressants and related compounds of biogenic amine uptake into rat brain synaptosomes: most antidepressants selectively block norepinephrine uptake. Eur. J. Phar. 104:277–286.
Pellegrino, L. J., Pellegrino, S. A., and Cushman, A. J. (eds) 1979. A stereotaxic atlas of the rat brain. Plenum Press, New York.
Paxinos, G., and Watson, C. (eds). 1986. The rat brain stereotaxic coordinates. Academic Press, San Diego, California.
Harik, S. I. 1984. Locus coeruleus lesion by local 6-OHDA infusion causes marked and specific destruction of noradrenergic neurons, long-term depletion of norepinephrine and the enzymes that synthesize it, and enhanced dopaminergic mechanisms in the ipsilateral cerebral cortex. J. Neurosci. 4:699–707.
Allin, R., Russell, V. A., Lamm, M. C. L., and Taljaard, J. J. F. 1988. Regional distribution of monoamines in the nucleus accumbens of the rat. Neurochem. Res. 13:937–942.
Gardner, C. R., Klein, J., and Grove, J. 1981. Endogenous GABA determines the characteristics of [3H]GABA-binding. Eur. J. Pharmacol. 75:83–92.
Bowery, N. G., Hill, D. R., and Hudson, A. L. 1983. Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes. Br. J. Pharmacol. 78:191–206.
Szekely, A. M., Barbaccia, M. L., and Costa, E. 1987. Effect of a protracted antidepressant treatment on signal transduction and [3H](−)-baclofen binding at GABAB receptors. J. Pharmacol. Exp. Ther. 243:155–159.
Miller, G. L. 1959. Protein determination for large numbers of samples. Analyt. Chem. 31:964.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Munson, P. J., and Rodbard, D. 1980. LIGAND: A versatile computerized approach for characterization of ligand-binding systems. Anal. Biochem. 107:220–239.
Weiss, G. K., Lewis, J., Jimenez-Rivera, C., Vigil, A., and Corcoran, M. E. 1990. Antikindling effects of locus coeruleus stimulation: mediation by ascending noradrenergic projections. Exp. Neurol. 108:136–140.
Engelbrecht, A. H., Russell, V., Carstens, M. E., de Villiers, A. S., Searson, A., Jaffer, A., and Taljaard, J. J. F. 1994. Evidence that noradrenergic neurons in the A1 and A2 nuclei are lesioned by low doses of 6-OHDA injected into the locus coeruleus. J. Neurosci. Methods (in press).
Adèr, J. P., Room, P., Postema, F., and Korf, J. 1980. Bilaterally diverging axon collaterals and contralateral projections from rat locus coeruleus neurons, demonstrated by fluorescent retrograde double labelling and norepinephrine metabolism. J. Neur. Trans. 49:207–218.
Loy, R., Koziel, D. A., Lindsey, J. D., and Moore, R. Y. 1980. Noradrenergic innervation of the adult rat hippocampal formation. J. Comp. Neurol. 189:699–710.
Suzdak, P. D., and Gianutsos, G. 1985. GABA-Noradrenergic interaction: Evidence for differential sites of action for GABA-A and GABA-B receptors. J. Neural. Transm. 64:163–172.
Karbon, E. W., Duman, R. S., and Enna, S. J. 1983. Biochemical identification of multiple GABAB binding sites: association with noradrenergic terminals in rat forebrain. Brain Res. 274:393–396.
Cross, J. A., and Horton, R. W. 1988. Effects of chronic oral administration of the antidepressants, desmethyl-imipramine and zimelidine on rat cortical GABAB binding sites: a comparison with 5-HT2 binding site changes. Br. J. Pharmacol. 93:331–336.
Borsini, F., Giuliani, S., and Meli, A. 1986. Functional evidence for altered activity of GABAergic receptors following chronic desipramine treatment in rats. J. Pharm. Pharmacol. 38:934–935.
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Engelbrecht, A.H., Russell, V.A. & Taljaard, J.J.F. Lack of effect of bilateral locus coeruleus lesion and antidepressant treatment on gamma-aminobutyric acidB receptors in the rat frontal cortex. Neurochem Res 19, 1119–1123 (1994). https://doi.org/10.1007/BF00965144
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DOI: https://doi.org/10.1007/BF00965144