Abstract
1. The effects of BTS 54,505, the primary amine metabolite of the non-tricylic putative antidepressant sibutramine, on the responses evoked by visual stimulation and ionophoretic application of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and excitatory amino acids (EAAs) in the rat dorsolateral geniculate nucleus (dLGN) have been investigated. 2. Ionophoretic application of 5-HT to dLGN neurones attenuated visually-evoked (n = 46), NMDA-evoked (n = 21) and AMPA-evoked responses (n = 21), while ionophoretic application of NA potentiated visually-evoked activity in these cells (n = 27). 3. Simultaneous application of BTS 54,505 with 5-HT (over 120 s) resulted in a prolongation of the recovery time (i.e. the period required by a neurone to recover by 50%, RT50) from the 5-HT-mediated suppression of discharge activity (approximately 275% increase in RT50). BTS 54,505 also prolonged the recovery time from a NA-mediated potentiation of firing (approximately 450% increase in RT50). These effects on recovery time are attributed to the inhibition of uptake of both 5-HT and NA by BTS 54,505. The amplitude of the response to 5-HT or NA was unaffected by co-ejection of BTS 54,505. 4. Ionophoretic application of N-methyl-D-aspartate (NMDA) produced a current-dependent increase in neuronal firing, as did application of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). A simultaneous 120 s application of BTS 54,505 inhibited the NMDA response in all cells studied (mean ED50 = 16 +/- 5 nA) but had no effect on AMPA-evoked activity in the majority of the same cells (n = 15/21).(ABSTRACT TRUNCATED AT 250 WORDS)
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- Alvarez F. J., Velasco A., Palomares J. L. Blockade of muscarinic, histamine H1 and histamine H2 receptors by antidepressants. Pharmacology. 1988;37(4):225–231. doi: 10.1159/000138470. [DOI] [PubMed] [Google Scholar]
- Buckett W. R., Thomas P. C., Luscombe G. P. The pharmacology of sibutramine hydrochloride (BTS 54 524), a new antidepressant which induces rapid noradrenergic down-regulation. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(5):575–584. doi: 10.1016/0278-5846(88)90003-6. [DOI] [PubMed] [Google Scholar]
- KANDEL E. R., SPENCER W. A. Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. J Neurophysiol. 1961 May;24:243–259. doi: 10.1152/jn.1961.24.3.243. [DOI] [PubMed] [Google Scholar]
- Kemp J. A., Foster A. C., Leeson P. D., Priestley T., Tridgett R., Iversen L. L., Woodruff G. N. 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6547–6550. doi: 10.1073/pnas.85.17.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leander J. D. Tricyclic antidepressants block N-methyl-D-aspartic acid-induced lethality in mice. Br J Pharmacol. 1989 Feb;96(2):256–258. doi: 10.1111/j.1476-5381.1989.tb11809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luscombe G. P., Hopcroft R. H., Thomas P. C., Buckett W. R. The contribution of metabolites to the rapid and potent down-regulation of rat cortical beta-adrenoceptors by the putative antidepressant sibutramine hydrochloride. Neuropharmacology. 1989 Feb;28(2):129–134. doi: 10.1016/0028-3908(89)90048-8. [DOI] [PubMed] [Google Scholar]
- Marwaha J., Aghajanian G. K. Relative potencies of alpha-1 and alpha-2 antagonists in the locus ceruleus, dorsal raphe and dorsal lateral geniculate nuclei: an electrophysiological study. J Pharmacol Exp Ther. 1982 Aug;222(2):287–293. [PubMed] [Google Scholar]
- Mason R. Circadian variation in sensitivity of suprachiasmatic and lateral geniculate neurones to 5-hydroxytryptamine in the rat. J Physiol. 1986 Aug;377:1–13. doi: 10.1113/jphysiol.1986.sp016172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer M. L., Westbrook G. L., Guthrie P. B. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature. 1984 May 17;309(5965):261–263. doi: 10.1038/309261a0. [DOI] [PubMed] [Google Scholar]
- McCaslin P. P., Yu X. Z., Ho I. K., Smith T. G. Amitriptyline prevents N-methyl-D-aspartate (NMDA)-induced toxicity, does not prevent NMDA-induced elevations of extracellular glutamate, but augments kainate-induced elevations of glutamate. J Neurochem. 1992 Aug;59(2):401–405. doi: 10.1111/j.1471-4159.1992.tb09385.x. [DOI] [PubMed] [Google Scholar]
- Nomura S., Zorn S. H., Enna S. J. Selective interaction of tricyclic antidepressants with a subclass of rat brain cholinergic muscarinic receptors. Life Sci. 1987 May 4;40(18):1751–1760. doi: 10.1016/0024-3205(87)90085-3. [DOI] [PubMed] [Google Scholar]
- Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
- Oye I., Paulsen O., Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-D-aspartate receptors. J Pharmacol Exp Ther. 1992 Mar;260(3):1209–1213. [PubMed] [Google Scholar]
- Reynolds I. J., Miller R. J. Tricyclic antidepressants block N-methyl-D-aspartate receptors: similarities to the action of zinc. Br J Pharmacol. 1988 Sep;95(1):95–102. doi: 10.1111/j.1476-5381.1988.tb16552.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogawski M. A., Aghajanian G. K. Norepinephrine and serotonin: opposite effects on the activity of lateral geniculate neurons evoked by optic pathway stimulation. Exp Neurol. 1980 Sep;69(3):678–694. doi: 10.1016/0014-4886(80)90060-6. [DOI] [PubMed] [Google Scholar]
- Sakurada K., Masu M., Nakanishi S. Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor. J Biol Chem. 1993 Jan 5;268(1):410–415. [PubMed] [Google Scholar]
- Scott G., Mason R. A simple and rapid method for improving recording characteristics using multibarrelled micropipettes. J Neurosci Methods. 1992 Jul;43(2-3):225–229. doi: 10.1016/0165-0270(92)90032-9. [DOI] [PubMed] [Google Scholar]
- Sernagor E., Kuhn D., Vyklicky L., Jr, Mayer M. L. Open channel block of NMDA receptor responses evoked by tricyclic antidepressants. Neuron. 1989 Mar;2(3):1221–1227. doi: 10.1016/0896-6273(89)90306-1. [DOI] [PubMed] [Google Scholar]
- Sillito A. M., Murphy P. C., Salt T. E., Moody C. I. Dependence of retinogeniculate transmission in cat on NMDA receptors. J Neurophysiol. 1990 Feb;63(2):347–355. doi: 10.1152/jn.1990.63.2.347. [DOI] [PubMed] [Google Scholar]
- Sillito A. M., Murphy P. C., Salt T. E. The contribution of the non-N-methyl-D-aspartate group of excitatory amino acid receptors to retinogeniculate transmission in the cat. Neuroscience. 1990;34(2):273–280. doi: 10.1016/0306-4522(90)90137-s. [DOI] [PubMed] [Google Scholar]
- Snyder S. H., Yamamura H. I. Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry. 1977 Feb;34(2):236–239. doi: 10.1001/archpsyc.1977.01770140126014. [DOI] [PubMed] [Google Scholar]
- Trullas R., Skolnick P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol. 1990 Aug 21;185(1):1–10. doi: 10.1016/0014-2999(90)90204-j. [DOI] [PubMed] [Google Scholar]
- Wang R. Y., de Montigny C., Gold B. I., Roth R. H., Aghajanian G. K. Denervation supersensitivity to serotonin in rat forebrain: single cell studies. Brain Res. 1979 Dec 14;178(2-3):479–497. doi: 10.1016/0006-8993(79)90708-x. [DOI] [PubMed] [Google Scholar]
- Watanabe Y., Saito H., Abe K. Tricyclic antidepressants block NMDA receptor-mediated synaptic responses and induction of long-term potentiation in rat hippocampal slices. Neuropharmacology. 1993 May;32(5):479–486. doi: 10.1016/0028-3908(93)90173-z. [DOI] [PubMed] [Google Scholar]
- White G., Lovinger D. M., Peoples R. W., Weight F. F. Inhibition of N-methyl-D-aspartate activated ion current by desmethylimipramine. Brain Res. 1990 Dec 24;537(1-2):337–339. doi: 10.1016/0006-8993(90)90381-k. [DOI] [PubMed] [Google Scholar]
