Abstract
The influence of repeated and single administrations of desipramine, amitryptiline, and mianserin on the EEG effects of clonidine has been investigated in rats implanted with chronic cortical electrodes. Clonidine induced a dose-dependent EEG synchronization in control animals. Signs of behavioral depression occurred after administration of moderate (0.1 mg/kg) and higher (0.2 mg/kg) doses of clonidine. Single doses of desipramine and amitryptiline attenuated the clonidine effect, while mianserine potentiated clonidine-induced synchronization. Antidepressants given once daily for 14 days completely (desipramine and amitryptiline) or partially (mianserin) reduced the effect of clonidine. Antidepressants alone produced only a slight effect on cortical EEG pattern.
Similar content being viewed by others
References
Baumann PA, Maitre L (1977) Blockade of presynaptic α receptors and of amine uptake in the rat brain by the antidepressant mainserine. Naunyn-Schmiedeberg's Arch Pharmacol 300: 31–37
Carlsson A, Corrodi H, Fuxe K, Hökfelt T (1969) Effect of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4-methyl-meta-tyrosine. Eur J Pharmacol 5: 367–373
Crews F, Schmith Ch (1978) Presynaptic alpha-receptor subsensitivity after long term antidepressant treatment. Science 202: 322–324
Dausse JP, Le Quan-Bul KH, Meyer P (1982) Alpha1 and alpha2-adrenoceptors in rat cerebral cortex: effects of neonatal treatment with 6-hydroxydopamine. Eur J Pharmacol 78: 15–20
Delbarre B, Schmitt H (1973) A further attempt to characterize sedative receptors activated by clonidine in chicken and mice. Eur J Pharmacol 22: 355–359
Delini-Stula A, Baumann P, Büch O (1977) Depression of exploratory activity by clonidine in rats as a model for the detection of relative pre- and postsynaptic central noradrenergic receptors selectivity of α adrenolytic drugs. Naunyn-Schmiedeberg's Arch Pharmacol 307: 115–122
Drew GM, Gower A, Marriott AS (1977) Pharmacological characterization of α adrenoceptors which mediate clonidine induced sedation. Br J Pharmacol 61: 468P
Dubocovich M, Langer SZ, Pelay F (1979) Cocaine and desipramine antagonize the clonidine-induced inhibition of 3H-noradrenaline release from the rat cerebral cortex. Br J Pharmacol 67: 417P-418P
Engberg G, Svensson TH (1980) Mianserin: direct activation of brain norepinephrine neurons by blocking α 2 receptors. Comm Psychopharm 4: 233–239
Engberg G, Elam M, Svensson TH (1982) Clonidine withdrawal: activation of brain noradrenergic neurons with specifically reduced α 2-receptor sensitivity. Life Sci 30: 235–243
Florio V, Bianchi L, Longo VG (1975) A study of the central effects of sympathomimetic drugs: EEG and behavioral investigations on clonidine and naphazoline. Neuropharmacology 14: 707–714
Franklin KB, Herberg LJ (1977) Presynaptic α adrenoceptors: the depression of self-stimulation by clonidine and its restoration by piperazine but not by phentolamine or phenoxybenzamine. Eur J Pharmacol 43: 33–38
Gower A, Marriott AS (1980) The inhibition of clonidine induced sedation in the mouse by antidepressant drugs. Br J Pharmacol 69: 287P
Kostowski W, Plaźnik A, Pucilowski O, Bidzinski A, Hauptmann M (1981) Lesion of serotonergic neurons antagonizes clonidine-induced suppression of avoidance behavior and locomotor activity in rats. Psychopharmacology 73: 261–264
Kostowski W, Malatyńska E (1983) Antagonism of behavioral depression produced by clonidine in the Mongolian gerbil: a potential screening test for antidepressant drugs. Psychopharmacology 79: 203–208
Langer SZ (1974) Presynaptic regulation of catecholamine release. Biochem Pharmacol 23: 529–538
Laverty R, Taylor KM (1969) Behavioral and biochemical effects of 2-(2,6-dichlorophenyloamino)-2-imidazoline hydrochloride (ST 155) on the central nervous system. Br J Pharmacol 35: 252–264
McMillen BA, Warnack W, German DC, Shore PA (1980) Effects of chronic desipramine treatment on rat brain noradrenergic responses to alpha-adrenergic drugs. Eur J Pharmacol 61: 239–246
Meddis R (1975) Statistical handbook for non-statisticians. McGraw Hill Book Company, London, pp 86–87
Meek J, Fuxe K, Anden N-E (1970) Effects of antidepressant drugs of the imipramine type on the central 5-hydroxytryptamine neurotransmission. Eur J Pharmacol 9: 325–332
Modigh K (1973) Effects of clomipramne (Anafranil) on neurotransmission in brain monoamine neurons. J Int Med Res 1: 274–280
Morris MJ, Elghozi JL, Dausse JP, Meyer P (1981) Alpha1 and alpha2 adrenoceptors in rat cerebral cortex: effect of frontal lobotomy. Naunyn-Schmiedeberg's Arch Pharmacol 316: 42–44
Nickolson VJ, Wieringa JH (1981) Presynaptic α block and inhibition of noradrenaline and 5-hyddroxytryptamine re-uptake by a series of compounds related to mianserin. J Pharm Pharmacol 33: 730–766
Palmer GC (1976) Influence of tricyclic antidepressants on the adenylate cyclase phosphodiesterase system in the rat cortex. Neuropharmacology 15: 1–7
Pasarelli F, Scotti de Carolis A (1982) Effects of chronic treatment with imipramine on the behavioral and electroencephalographic modifications induced by clonidine in the rat. Neuropharmacology 21: 591–593
Pasarelli F, Scotti de Carolis A (1983) Effects of chronic treatment with imipramine, trazodone and electroshock on the behavioral and electroencephalographic modifications induced by clonidine in the rat. Neuropharmacology 22: 785–789
Peroutka SJ, Snyder SH (1980) Chrońic antidepressant treatment lowers spiroperidol-labeled serotonin receptor binding. Science 210: 88–90
Robson RD, Antonaccio MJ, Salenes JK, Lebman J (1978) Antagonism by mianserin and classical α adrenoceptor blocking drugs on some cardiovascular and behavioral effects of clonidine. Eur J Pharmacol 47: 431–442
Scuveè-Moreau JJ, Svensson TH (1982) Sensitivity in vivo of central α 2 and opiate receptors after chronic treatment with various antidepressants. J Neural Transm 54: 51–63
Spyraki Ch, Fibiger HC (1980) Functional evidence for subsensitivity of noradrenergic α 2 receptors after chronic desipramine treatment. Life Sci 27: 1863–1867
Starke K, Montel H, Endo T (1975) Relative potenties of sympathomimetic drugs in pre- and postsynaptic adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 287: R5
Starke K (1978) Presynaptic regulation of release of noradrenaline in the central nervous system. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon Press, Oxford, pp 143–183
Sugrue MF (1980) The inability of chronic mianserin to block central α 2 adrenoceptors. Eur J Pharmacol 68: 377–380
Sugrue MF (1983) Chronic antidepressant therapy and associated changes in central monoaminergic receptor functioning. Pharmacol Ther 21: 1–33
Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the α adrenergic agonist clonidine. Brain Res 92: 291–305
Svensson TH, Usdin T (1978) Feedback inhibition of brain noradrenaline neurons by tricyclic antidepressants: α receptor mediation. Science 202: 1089–1091
Tang SW, Seeman P (1980) Effect of antidepressant drugs on serotonergic and adrenergic receptors. Naunyn-Schmiedeberg's Arch Pharmacol 311: 255–261
Taylor JE, Richelson F (1980) High affinity binding of tricyclic antidepressants to histamine H1 receptors: fact and artifact. Eur J Pharmacol 67: 41–46
U'Prichard DC, Greenberg D, Sheehan P, Snyder SH (1978) Tricyclic antidepressants: therapeutic properties and affinity for α noradrenergic receptor binding sites in the brain. Science 199: 197–198
U'Prichard DC, Bechtel WD, Rouot BM, Snyder SH (1979) Multiple apparent alpha-noradrenergic receptor binding sites in rat brain: effect of 6-hydroxydopamine. Mol Pharmacol 16: 47–60
Voiglander PF von, Triezenberg HJ, Losey EG (1978) Interactions between clonidine and antidepressant drugs: a method for identifying antidepressant-like agents. Neuropharmacology 17: 375–381
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kostowski, W., Dyr, W. & Zacharski, B. A study of the effects of clonidine on the EEG in rats treated with single and multiple doses of antidepressants. Psychopharmacology 84, 85–90 (1984). https://doi.org/10.1007/BF00432031
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00432031