Abstract
1. The effects of chronic administration of five antidepressant drugs on the benzodiazepine and 5-HT2A binding sites in the same rat brain were assessed.
2. Clomipramine, desipramine, maprotiline, fluoxetine, and phenelzine (all 10 mg/kg/day) were administered s.c. for 21 days by Alzet osmotic minipumps.
3. Results showed that none of the drugs changed the density or affinity of benzodiazepine binding sites, yet at the same dose all the drugs with the exception of fluoxetine decreased binding to 5-HT2A receptors in the same animals.
Key words: antidepressants, benzodiazepine receptors, clomipramine, desipramine, fluoxetine, 5-hydroxytryptamine receptors, maprotiline, phenelzine
References
- Allison, K., Paetsch, P. R., Baker, G. B., and Greenshaw, A. J. (1993). Chronic antidepressant drug treatment attenuates motor-suppresant effects of apomorphine without changing3H-GBR 12935 binding.Eur. J. Pharmacol.249125–131. [DOI] [PubMed] [Google Scholar]
- Aspeslet, L. J. (1994).Chirality and Metabolism: Studies on the Antidepressants rac-Tranylcypromine and rac-Fluoxetine, Ph.D thesis, University of Alberta, Edmonton, AB. [Google Scholar]
- Baker, G. B., and Dewhurst, W. G. (1985). Biochemical theories of affective disorders. InPharmacotherapy of Affective Disorders (W. G. Dewhurst and G. B. Baker, Eds.), New York University Press, New York, pp. 1–59. [Google Scholar]
- Baker, G. B., and Greenshaw, A. J. (1989). Effects of long-term administration of antidepressants and neuroleptics on receptors in the central nervous system.Cell. Mol. Neurobiol.91–44. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baron, B., Ogden, A., Siegel, B., Stegeman, J., Ursillo, R., and Dudley, M. (1988). Rapid down-regulation of beta-adrenoceptors by coadministration of desipramine and fluoxetine.Eur. J. Pharmacol.154125–134. [DOI] [PubMed] [Google Scholar]
- Bel, N., and Artigas, F. (1993). Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphé nuclei.Synapse15243–245. [DOI] [PubMed] [Google Scholar]
- Blier, P., and de Montigney, C. (1994). Current advances and trends in the treatment of depression.Trends Pharmacol. Sci.,15220–226. [DOI] [PubMed] [Google Scholar]
- Briley, M., and Moret, C. (1993). Neurobiological mechanisms involved in antidepressant therapeis.Clin. Neuropharmacol.16387–400. [DOI] [PubMed] [Google Scholar]
- Bunney, W. E., and Davis, J. M. (1965). Norepinephrine in depressive reactions. A review.Arch. Gen. Psychiat.13483–494. [DOI] [PubMed] [Google Scholar]
- Burnet, P. W. J., Michelson, D., Smith, M. A., Gold, P. W., and Sternberg, E. M. (1994). The effect of chronic imipramine administration on the densities of 5-HT1A and 5-HT2 receptors and the abundancies of 5-HT receptor and transporter mRNA in the cortex, hippocampus and dorsal raphe of three strains of rat.Brain Res.638311–324. [DOI] [PubMed] [Google Scholar]
- Cadogan, A. K., Marsden, C. A., Tulloch, I., and Kendall, D. A. (1993). Evidence that chronic administration of paroxetine or fluoxetine enhances 5-HT2-receptor function in the brain of the guinea pig.Neuropharmacology32249–256. [DOI] [PubMed] [Google Scholar]
- Cheetham, S. C., Crompton, M. R., Katona, C. L. E., and Horton, R. W. (1988). Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims.Brain Res.460114–123. [DOI] [PubMed] [Google Scholar]
- Cross, J. A., and Horton, R. W. (1987). Are increases in GABAB receptors consistent findings following chronic antidepressant administration?Eur. J. Pharmacol.141159–162. [DOI] [PubMed] [Google Scholar]
- Deakin, J. F. W. (1988). 5-HT2 receptors, depression and anxiety.Pharmacol. Biochem. Behav.29819–820. [DOI] [PubMed] [Google Scholar]
- Doble, A., and Martin, I. L. (1992). Multiple benzodiazepine receptors: No reason for anxiety.Trends Pharmacol. Sci.1376–81. [DOI] [PubMed] [Google Scholar]
- Drebit, R., Baker, G. B., and Dewhurst, W. G. (1988). Determination of maprotiline and desmethylmaprotiline in plasma and urine by gas-liquid chromatolgraphy with nitrogen-phosphorus detection.J. Chromatogr. Biomed. Appl.432334–339. [DOI] [PubMed] [Google Scholar]
- Eison, A. S., Yocca, F. D., and Gianutsos, G. (1991). Effect of chronic administration of antidepressant drugs on 5-HT2 mediated behavior in the rat following noradrenergic or serotonergic denervation.J. Neural Transm.,8419–32. [DOI] [PubMed] [Google Scholar]
- Fuxe, K., Ogren, S., Agnoti, L., Benfenati, F., Fredholm, B., Andersson, K., Zini, I., and Eneroth, P. (1983). Chronic antidepressant treatment and central 5-HT synapses.Neuropharmacology22389–400. [DOI] [PubMed] [Google Scholar]
- Giardino, L., Zanni, M., Velardo, A., Amato, G., and Calza, L. (1993). Effect of sertraline treatment on benzodiazepine receptors in the rat brain.J. Neural Transm.9431–41. [DOI] [PubMed] [Google Scholar]
- Goodnough, D. B., and Baker, G. B. (1994). 5-HT2 and beta-adrenergic receptor regulation in rat brain following chronic treatment with desipramine and fluoxetine alone and in combination.J. Neurochem.622262–2268. [DOI] [PubMed] [Google Scholar]
- Heninger, C., Saito, N., Tallman, J. F., Carrett, K. M., Vitek, M. P., Duman, R. S., and Gallager, D. W. (1990). Effects of continuous diazepam administration on GABAA subunit mRNA in rat brain.J. Mol. Neurosci.2101–107. [DOI] [PubMed] [Google Scholar]
- Hrdina, P. D. (1993). Is there action beyond receptors?J. Psychiatr. Neurosci.1857–69. [PMC free article] [PubMed] [Google Scholar]
- Hrdina, P. D., and Vu, T. B. (1993). Chronic fluoxetine treatment upregulates 5-HT uptake sites and 5-HT2 receptors in rat brain: an autoradiographic study.Synapse14324–331. [DOI] [PubMed] [Google Scholar]
- Humphrey, P. P. A., Hartig, P., and Hoyer, D. (1993). A proposed new nomenclature for 5-HT receptors.Trends Pharmacol. Sci.14233–236. [DOI] [PubMed] [Google Scholar]
- Hyttel, J. (1994). Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs).Int. Clin. Psychopharmacol.919–26. [DOI] [PubMed] [Google Scholar]
- Kang, I., and Miller, L. G. (1991). Decreased GABAA receptor subunit mRNA concentrations following chronic lorazepam administration.Br. J. Pharmacol.1031285–1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellar, K. J., Cascio, C. S., Butler, K. R., and Kurtzke, R. N. (1981). Differential effects of electroconvulsive shock and antidepressant drugs on serotonin2 receptors in rat brain.Eur. J. Pharmacol.69515–518. [DOI] [PubMed] [Google Scholar]
- Kendall, D. A., and Nahorski, S. R. (1985). 5-Hydroxytryptamine-stimulated inositol phospholipid hydrolysis in rat cerebral cortex slices: Pharmacological characterization and effects of antidepressants.J. Pharmacol. Exp. Ther.233473–479. [PubMed] [Google Scholar]
- Kimber, J. R., Cross, J. A., and Horton, R. W. (1987). Benzodiazepine and GABAA receptors in rat brain following chronic antidepressant drug administration.Biochem. Pharmacol.364175–4176. [DOI] [PubMed] [Google Scholar]
- Klimek, V., Zak-Knapik, J., and Mackowiak, M. (1994). Effects of repeated treatment with fluoxetine and citalopram, 5-HT uptake inhibitors, on 5-HT1A and 5-HT2 receptors in the rat brain.J. Psychiatr. Neurosci.1963–67. [PMC free article] [PubMed] [Google Scholar]
- Lafaille, F., Welner, S. A., and Suryani-Cadotte, B. E. (1991). Regulation of serotonin type 2 (5-HT2) andβ-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment.J. Psychiatr. Neurosci.16209–214. [PMC free article] [PubMed] [Google Scholar]
- Lapin, I. P., and Oxenkrug, G. F. (1969). Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect.Lanceti132–136. [DOI] [PubMed] [Google Scholar]
- Lesch, K. P., Hough, C. J., Aulakh, C. S., Wolozin, B. L., Tolliver, T. J., Hill, J. L., Akiyoshi, J., Chuang, D. M., and Murphy, D. L. (1992). Fluoxetine modulates G proteinαs,αq, andα12 subunit messenger RNA expression in rat brain.Eur. J. Pharmacol. Mol. Pharmacol.227233–237. [DOI] [PubMed] [Google Scholar]
- Li, Q., Brownfield, M. S., Battaglia, G., Cabrera, T. M., Levy, A. D., Rittenhouse, P. A., and van de Kar, L. D. (1993). Long-term treatment with the antidepressents fluoxetine and desipramine potentiates endocrine responses to the serotonin agonists 6-chloro-2[1-piperazinyl]pyrazine (MK-212) and (±)-1-(2,5-dimethyoxy-4-iodophenyl)-2-aminopropane HCl (DOI).J. Pharmacol. Exp. Ther.266836–844. [PubMed] [Google Scholar]
- Lloyd, K. G., Thuret, F., and Pilc, A. (1985). Upregulation of gamma-aminobutyric acid GABAB binding sites in rat frontal cortex: A common action of repeated administration of different classes of antidepressants and electroshock.J. Pharmacol. Exp. Ther.234191–199. [PubMed] [Google Scholar]
- Lloyd, K. G., Zivkovic, B., Scatton, B., Morselli, P. L., and Bartholini, G. (1989). The GABAergic hypothesis of depression.Prog. Neuro-Psychopharmacol. Biol. Psychiat.13341–351. [DOI] [PubMed] [Google Scholar]
- Lowther, S., De Paermentier, F., Crompton, M. R., Katona, C. L. E., and Horton, R. W. (1994). Brain 5-HT2 receptors in suicide victims: Violence of death, depression and effects of antidepressant treatment.Brain Res.642281–289. [DOI] [PubMed] [Google Scholar]
- Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurements with the folin phenol reagent.J. Biol. Chem.193265–275. [PubMed] [Google Scholar]
- Mann, C. D., Vu, T. B., and Hrdina, P. D. (1995). Protein kinase C in rat brain cortex and hippocampus: Effect of chronic treatment with desipramine and fluoxetineBr. J. Pharmacol.,115 (in press). [DOI] [PMC free article] [PubMed]
- McKenna, K. F., McManus, D., Baker, G. B., and Coutts, R. T. (1994). Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: Effects on GABAergic function.J. Neural Transm.41 (Suppl):115–122. [DOI] [PubMed] [Google Scholar]
- McManus, D. J. (1992).Effects of Chronic Antidepressant Drug Administration on GABAergic Mechanisms in Rat Brain, Ph.D. thesis, University of Alberta, Edmonton, AB. [Google Scholar]
- McManus, D., and Greenshaw, A. J. (1991). Differential effects of antidepressants on GABAB andβ-adrenergic receptors in rat cerebral cortex.Biochem. Pharmacol.421525–1528. [DOI] [PubMed] [Google Scholar]
- Nayeem, N., Green, T. P., Martin, I. L., and Barnard, E. A. (1994). Quatenary structure of the native GABA-A receptor determined by electron microscopic image analysis.J. Neurochem.62815–818. [DOI] [PubMed] [Google Scholar]
- Papp, M., Klimek, V., and Willner, P. (1994). Effects of imipramine on serotonergic andβ-adrenergic receptor binding on a realistic animal model of depression.Psychopharmacology114309–314. [DOI] [PubMed] [Google Scholar]
- Paul, I. A., Duncan, G. E., Powell, K. R., Mueller, R. A., Hong, J. S., and Breese, G. R. (1988). Regionally specific neural adaptation ofβ-adrenergic and 5-hydroxytryptamine2 receptors after antidepressant administration in the forced swim test and after chronic antidepressant drug treatment.J. Pharmacol. Exp. Ther.246956–962. [PubMed] [Google Scholar]
- Peroutka, S. J., and Snyder, S. H. (1980). Long-term antidepressant treatment decreases spiroperidol-labelled serotonin receptor binding.Science21088–90. [DOI] [PubMed] [Google Scholar]
- Petty, F., Kramer, G. L., and Hendrickse, W. (1993). GABA and depression. InBiology of Depressive Disorders, Part A: A Systems Perspective (J. J. Mann and D. J. Kupfer, Eds.), Plenum Press, New York, Chap. 4. [Google Scholar]
- Primus, R. J., and Gallager, D. W. (1992). GABAA receptor subunit mRNA levels are differentially influed by chronic FG7142 and diazepam exposure.Eur. J. Pharmacol. (Mol. Pharmacol.)22621–28. [DOI] [PubMed] [Google Scholar]
- Pritchett, D. B., Sontheimer, H., Shivers, B. D., Ymer, S., Kettenmann, H., Schofield, P. R., and Seeberg, P. H. (1989). Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology.Nature338582–585. [DOI] [PubMed] [Google Scholar]
- Przegalinski, E., Rokosz-Pelc, A., Baran, L., and Vetulani, J. (1987). Repeated treatment with antidepressant drugs does not affect the benzodiazepine receptors in preincubated membrane preparations from mouse and rat brain.Pharmacol. Biochem. Behav.2635–36. [DOI] [PubMed] [Google Scholar]
- Richards, G., Schoch, P., and Haefely, W. (1991). Benzodiazepine receptors: New vistas.Sem. Neurosci.3191–203. [Google Scholar]
- Sanders-Bush, E., Breeding, M., Knoth, K., and Tsutsumi, M. (1989). Sertraline-induced desensitization of the serotonin 5HT-2 receptor transmembrane signaling system.Psychopharmacology9964–69. [DOI] [PubMed] [Google Scholar]
- Schildkraut, J. J. (1965). The catecholamine hypothesis of affective disorders: A review of supporting evidence.Am. J. Psychiat.122509–522.5319766 [Google Scholar]
- Stocks, G. M., Cheetham, S. C., Crompton, M. R., Katona, C. L. E., and Horton, R. W. (1990). Benzodiazepine binding sites in amygdala and hippocampus of depressed suicide victims.J. Affect. Disord.1811–15. [DOI] [PubMed] [Google Scholar]
- Suranyi-Cadotte, B. E., Dam, T. V., and Quirion, R. (1985). Antidepressant-anxiolytic interaction density of benzodiazepine receptors in rat brain following chronic administration of antidepressants.Eur. J. Pharmacol.106673–675. [DOI] [PubMed] [Google Scholar]
- Suzdak, P. D., and Gianutsos, G. (1986). Effect of chronic imipramine or baclofen on GABAB binding and cyclic AMP production in cerebral cortex.Eur. J. Pharmacol.131129–133. [DOI] [PubMed] [Google Scholar]
- Wamsley, J. K., Byerley, W. F., McCabe, R. T., McConnell, E. J., Dawson, T. M., and Grosser, B. I. (1987). Receptor alterations associated with serotonergic agents: An autoradiographic analysis.J. Clin. Psychiat.48 (Suppl): 19–25. [PubMed] [Google Scholar]
- Watanabe, Y., Saki, R. R., McEwen, B. S., and Mendelson, S. (1993). Stress and antidepressant effects on hippocampal and cortical 5-HT(1A) and 5-HT(2) receptors and transport sites for serotonin.Brain Res.61587–94. [DOI] [PubMed] [Google Scholar]
- Wieland, S., Fischette, C. T., and Lucki, I. (1993). Effect of chronic treatments with tandospirone and imipramine on serotonin-mediated behavioural responses and monoamine receptors.Neuropharmacology32561–573. [DOI] [PubMed] [Google Scholar]
- Wurtman, R. J., and Axelrod, J. (1963). A sensitive and specific assay for the estimation of monoamine oxidase.Biochem. Pharmacol.121439–1441. [DOI] [PubMed] [Google Scholar]