Abstract
It has been shown recently that chronic administration of tricyclic antidepressant drugs results in enhanced responsiveness of neurones to iontophoretically applied 5-hydroxytryptamine (5-HT) in rat forebrain regions. The present investigation tested whether this effect is accompanied by an enhancement of behavioral effects of the amine. Behavioral signs of sleep in young chicks following systemic administration of 5-HT were used as an index of the action of the amine at central receptor sites. Imipramine, desipramine, amitryptiline, pizotifen, and mianserin given 30 min before 5-HT all reduced the duration of 5-HT-induced behavioral depression. However, 6–8 day pretreatment with the same drugs resulted in an increased duration of the 5-HT-induced depression. The results suggest that the antidepressant drugs can block 5-HT receptors in the central nervous system (CNS) and that chronic blockade resulting from repeated administration of the drugs results in an increase in number or sensitivity of 5-HT receptors.
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Aprison, M. H., Takahashi, R., Tachiki, K.: Hypersensitive serotonergic receptors involved in clinical depression: A theory. In: Neuropharmacology and behaviour, B. Haber, M. H. Aprison, eds., pp. 23–53. New York: Plenum 1978
Banerjee, S. P., Kung, S. L., Riggi, S. J., Chanda, S. K.: Development of β-adrenergic receptor subsensitivity by antidepressants. Nature 268, 455–456 (1977)
Bennet, J. L., Aghajanian, G. K.: D-LSD binding to brain homogenates: Possible relationship to serotonin receptors. Life Sci. 15, 1935–1944 (1974)
Bergstrom, D. A., Kellar, K. J.: Adrenergic and serotonergic receptor binding in rat brain after chronic desmethylimipramine treatment. J. Pharmacol. Exp. Ther. 209, 256–261 (1979)
Bradshaw, C. M., Roberts, M. H. T., Szabadi, E.: Effects of imipramine and desipramine on responses of single cortical neurons to noradrenaline and 5-hydroxytryptamine. Br. J. Pharmacol. 52, 349–358 (1974)
Clements-Jewry, S.: The development of cortical β-adrenoreceptor subsensitivity in the rat by chronic treatment with trazadone, doxepin and mianserin. Neuropharmacology 17, 779–781 (1978)
Coppen, A.: The biochemistry of affective disorders. Br. J. Psychiatry 113, 1237 (1967)
Davis, J. A.: Theories of the biological aetiology of affective disorders. Int. Rev. Neurobiol. 12, 145–175 (1970)
De Montigny, C., Aghajanian, G. K.: Tricyclic antidepressants: Long-term treatment increases responsitivity of rat forebrain neurones to serotonin. Science 202, 1303–1306 (1978)
Dixon, A. K., Hill, R. C., Roemer, D., Scholtysik, G.: Pharmacological properties of 4-(1-methyl-4-piperidylidine) 9, 10-dihydro-4-H-benzo-4,5-cyclohepta-1,2-thiophene hydrogen maleate (Pizotifen). Arzneim. Forsch. 27, 1968–1979 (1977)
Domenjoz, R., Theobold, W.: Zur Pharmakologie des Tofranil (N-3-dimethylaminopropyl-imino-dibenzyl-hydrochlorid). Arch. Int. Pharmacodyn. Ther. 120, 450–489 (1959)
Friedman, E., Dallob, A.: Enhanced serotonin receptor activity after chronic treatment with imipramine or amitryptyline. Commun. Psychopharmacol. 3, 89–92 (1979)
Fügner, A.: Antagonism of the drug-induced behavioural sleep in chicks. Arzneim. Forsch. 9, 1350–1352 (1971)
Garver, D. L., Davis, J. M.: Biogenic amine hypotheses of affective disorders. Life Sci. 24, 383–394 (1979)
Hehman, B. S., Vonderahe, M. D., Peters, J. J.: Effect of serotonin on behaviour, electrical activity of the brain and seizure threshold of the newly hatched chick. Neurology 11, 1011–1016 (1961)
Jalfre, M., Ruch-Monachon, M. A., Haefely, W.: Methods for assessing the interactions of agents with 5-hydroxytryptamine neurones and receptors in the brain. Adv. Biochem. Psychopharmacol. 10, 121–134 (1974)
Kramer, S. Z., Seifter, J.: The effects of GABA and biogenic amines on behaviour and brain electrical activity in chicks. Life Sci. 5, 527–534 (1966)
Leonard, B. L.: Some effects of a new tetracyclic antidepressant compound, OrgGB94, on the metabolism of monoamines in the rat brain. Psychopharmacologia 36, 221–236 (1974)
Mogilinicka, E., Klimek, V.: Mianserin, danitracen and amitriptyline withdrawal increases the behavioural responses of rats to L-5-HTP. J. Pharm. Pharmacol. 31, 704–705 (1979)
Przegalinski, E., Baran, L., Palider, W., Siwanowicz, J.: The central action of pizotifen. Psychopharmacology 62, 295–300 (1979)
Ross, S. B., Renyi, A. L.: Inhibition of the uptake of 3H-catecholamines by antidepressants and related drugs. Eur. J. Pharmacol. 2, 181–186 (1967)
Ross, S. B., Renyi, A. L.: Inhibition of the uptake of 3H-5-HT in brain slices. Life Sci. 7, 270–277 (1969)
Spooner, C. E., Winters, W. D.: Evidence for a direct action of monoamines on the chick CNS. Experientia 21, 256–258 (1965)
Trulson, M. E., Stark, A. D., Jacobs, B. L.: Lack of supersensitivity to L-5-hydroxytryptophan following chronic methysergide treatment. J. Pharm. Pharmacol. 29, 382–384 (1977)
Vargaftig, B. B., Coignet, J. L., DeVos, C. J., Grijsen, H., Bonta, I. L.: Mianserin hydrochloride: Peripheral and central effects in relation to antagonism against 5-hydroxytryptamine and tryptamine. Eur. J. Pharmacol. 16, 336–346 (1971)
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Jones, R.S.G. Enhancement of 5-Hydroxytryptamine-induced behavioral effects following chronic administration of antidepressant drugs. Psychopharmacology 69, 307–311 (1980). https://doi.org/10.1007/BF00433101
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DOI: https://doi.org/10.1007/BF00433101