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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Perspective

From Inhibition of GABA-A Receptor-Mediated Synaptic Transmission by Conventional Antidepressants to Negative Allosteric Modulators of Alpha5- GABA-A Receptors as Putative Fast-Acting Antidepressant Drugs: Closing the Circle?

Author(s): Alberto Fernández-Teruel*

Volume 20, Issue 1, 2022

Page: [85 - 89] Pages: 5

DOI: 10.2174/1570159X19666211104144650

Abstract

The present perspective paper shortly and specifically addresses the issues of whether inhibition of GABA-A receptor-mediated synaptic transmission may be involved in antidepressantlike actions and the therapeutic effects of conventional antidepressant (AD) drugs, and whether the recent development of negative allosteric modulators (NAMs) of the alpha5-GABA-A receptor may constitute significant progress in our knowledge on the neurobiology and the treatment of depression.

Keywords: GABA-A transmission, conventional antidepressants, antidepressant drugs, modulators of alpha5-GABA-A, GABA-A receptors, negative allosteric modulators.

[1]
Suzdak, P.D.; Gianutsos, G. Parallel changes in the sensitivity of gamma-aminobutyric acid and noradrenergic receptors following chronic administration of antidepressant and GABAergic drugs. A possible role in affective disorders. Neuropharmacology, 1985, 24(3), 217-222.
[http://dx.doi.org/10.1016/0028-3908(85)90077-2] [PMID: 2986038]
[2]
Suranny-Cadotte, B.E.; Dam, T.V.; Quirion, R. Antidepressant- anxiolytic interaction: decreased density of benzodiazepine receptors in rat brain following chronic administration of antidepressants. Eur. J. Pharmacol., 1985, 106, 673-675.
[http://dx.doi.org/10.1016/0014-2999(84)90079-7]
[3]
Barbaccia, M.L.; Ravizza, L.; Costa, E. Maprotiline: An antidepressant with an unusual pharmacological profile. J. Pharmacol. Exp. Ther., 1986, 236(2), 307-312.
[PMID: 3003338]
[4]
Squires, R.F.; Saederup, E. Antidepressants and metabolites that block GABAA receptors coupled to 35S-t-butylbicyclophosphorothionate binding sites in rat brain. Brain Res., 1988, 441(1-2), 15-22.
[http://dx.doi.org/10.1016/0006-8993(88)91378-9] [PMID: 2833998]
[5]
Malatynska, E.; Knapp, R.J.; Ikeda, M.; Yamamura, H.I. Antidepressants and seizure-interactions at the GABA-receptor chloride-ionophore complex. Life Sci., 1988, 43(4), 303-307.
[http://dx.doi.org/10.1016/0024-3205(88)90107-5] [PMID: 2456440]
[6]
Fernández Teruel, A.; Longoni, B.; Corda, M.G. Imipramine and GABA-stimulated chloride uptake in rat cortex. Biol. Psychiatry, 1989, 25(7), 971-974.
[http://dx.doi.org/10.1016/0006-3223(89)90277-1] [PMID: 2541804]
[7]
Fernández-Teruel, A.; Escorihuela, R.M.; Boix, F.; Longoni, B.; Corda, M.G.; Tobeña, A. Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats. Neuropsychobiology, 1990-1991b, 23(3), 147-152.
[http://dx.doi.org/10.1159/000119442] [PMID: 1965914]
[8]
Fernández-Teruel, A.; Escorihuela, R.M.; Boix, F.; Tobeña, A. Picrotoxin changes the effects of imipramine and desipramine in rats in the forced swimming test. Eur. J. Pharmacol., 1990, 181(1-2), 35-41. a
[http://dx.doi.org/10.1016/0014-2999(90)90242-X] [PMID: 2387320]
[9]
Cannizzaro, G.; Flugy, A.; Cannizzaro, C.; Gagliano, M.; Sabatino, M. Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenetetrazol. Eur. Neuropsychopharmacol., 1993, 3(4), 477-484.
[http://dx.doi.org/10.1016/0924-977X(93)90272-N] [PMID: 8111220]
[10]
Cannizzaro, C.; Cannizzaro, E.; Gagliano, M.; Mineo, A.; Sabatino, M.; Cannizzaro, G. Effects of desipramine and alprazolam on forced swimming behaviour of adult rats exposed to prenatal diazepam. Eur. J. Pharmacol., 1995, 273(3), 239-245.
[http://dx.doi.org/10.1016/0014-2999(94)00690-9] [PMID: 7737331]
[11]
Dennis, T.; Beauchemin, V.; Lavoie, N. Antidepressant-induced modulation of GABAA receptors and beta-adrenoceptors but not GABAB receptors in the frontal cortex of olfactory bulbectomised rats. Eur. J. Pharmacol., 1994, 262(1-2), 143-148.
[http://dx.doi.org/10.1016/0014-2999(94)90037-X] [PMID: 7813565]
[12]
Aricioglu, F.; Altunbas, H. Harmane induces anxiolysis and antidepressant-like effects in rats. Ann. N. Y. Acad. Sci., 2003, 1009, 196-201.
[http://dx.doi.org/10.1196/annals.1304.024] [PMID: 15028588]
[13]
Farzin, D.; Mansouri, N. Antidepressant-like effect of harmane and other beta-carbolines in the mouse forced swim test. Eur. Neuropsychopharmacol., 2006, 16(5), 324-328.
[http://dx.doi.org/10.1016/j.euroneuro.2005.08.005] [PMID: 16183262]
[14]
Nishimura, H.; Ida, Y.; Tsuda, A.; Tanaka, M. Opposite effects of diazepam and beta-CCE on immobility and straw-climbing behavior of rats in a modified forced-swim test. Pharmacol. Biochem. Behav., 1989, 33(1), 227-231.
[http://dx.doi.org/10.1016/0091-3057(89)90454-1] [PMID: 2506583]
[15]
Jacob, T.C. Neurobiology and therapeutic potential of α5-GABA Type A receptors. Front. Mol. Neurosci., 2019, 12, 179.
[http://dx.doi.org/10.3389/fnmol.2019.00179] [PMID: 31396049]
[16]
Martin, L.J.; Bonin, R.P.; Orser, B.A. The physiological properties and therapeutic potential of α5-GABAA receptors. Biochem. Soc. Trans., 2009, 37(Pt 6), 1334-1337.
[http://dx.doi.org/10.1042/BST0371334] [PMID: 19909271]
[17]
Mohamad, F.H.; Has, A.T.C. The α5-Containing GABAA receptors-a brief summary. J. Mol. Neurosci., 2019, 67(2), 343-351.
[http://dx.doi.org/10.1007/s12031-018-1246-4] [PMID: 30607899]
[18]
Fogaça, M.V.; Duman, R.S. Cortical GABAergic dysfunction in stress and depression: new insights for therapeutic interventions. Front. Cell. Neurosci., 2019, 13, 87.
[http://dx.doi.org/10.3389/fncel.2019.00087] [PMID: 30914923]
[19]
Olsen, R.W. GABAA receptor: positive and negative allosteric modulators.Neuropharmacology, 2018, 136(Pt A), 10-22.
[http://dx.doi.org/10.1016/j.neuropharm.2018.01.036]
[20]
Atack, J.R.; Maubach, K.A.; Wafford, K.A.; O’Connor, D.; Rodrigues, A.D.; Evans, D.C.; Tattersall, F.D.; Chambers, M.S.; MacLeod, A.M.; Eng, W-S.; Ryan, C.; Hostetler, E.; Sanabria, S.M.; Gibson, R.E.; Krause, S.; Burns, H.D.; Hargreaves, R.J.; Agrawal, N.G.B.; McKernan, R.M.; Murphy, M.G.; Gingrich, K.; Dawson, G.R.; Musson, D.G.; Petty, K.J. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J. Pharmacol. Exp. Ther., 2009, 331(2), 470-484.
[http://dx.doi.org/10.1124/jpet.109.157636] [PMID: 19704033]
[21]
Fischell, J.; Van Dyke, A.M.; Kvarta, M.D.; LeGates, T.A.; Thompson, S.M. Rapid antidepressant action and restoration of excitatory synaptic strength after chronic stress by negative modulators of alpha5-containing GABAA receptors. Neuropsychopharmacology, 2015, 40(11), 2499-2509.
[http://dx.doi.org/10.1038/npp.2015.112] [PMID: 25900119]
[22]
Samardžić, J.; Puškaš, L.; Obradović, M.; Lazić-Puškaš, D.; Obradović, D. Antidepressant effects of an inverse agonist selective for α5 gaba-a receptors in the rat forced swim test. Acta Vet. (Beogr.), 2014, 64, 52-60.
[http://dx.doi.org/10.2478/acve-2014-0006]
[23]
Zanos, P.; Nelson, M.E.; Highland, J.N.; Krimmel, S.R.; Georgiou, P.; Gould, T.D.; Thompson, S.M. negative allosteric modulator for 5 subunit-containing GABA receptors exerts a rapid and persistent antidepressant-like action without the side effects of the nmda receptor antagonist ketamine in mice. eNeuro,, 2017, 4(1), 0285-0216.
[http://dx.doi.org/10.1523/ENEURO.0285-16.2017]
[24]
Xiong, Z.; Zhang, K.; Ishima, T.; Ren, Q.; Chang, L.; Chen, J.; Hashimoto, K. Comparison of rapid and long-lasting antidepressant effects of negative modulators of α5-containing GABAA receptors and (R) ketamine in a chronic social defeat stress model. Pharmacol. Biochem. Behav., 2018, 175, 139-145.
[http://dx.doi.org/10.1016/j.pbb.2018.10.005] [PMID: 30359627]
[25]
Carreno, F.R.; Collins, G.T.; Frazer, A.; Lodge, D.J. Selective pharmacological augmentation of hippocampal activity produces a sustained antidepressant-like response without abuse-related or psychotomimetic effects. Int. J. Neuropsychopharmacol., 2017, 20(6), 504-509.
[http://dx.doi.org/10.1093/ijnp/pyx003] [PMID: 28339593]
[26]
Bugay, V.; McCoy, A.M.; Lodge, D.J.; Brenner, R.; Frazer, A.; Carreno, F.R. Mechanisms associated with the antidepressant-like effects of L-655,708. Neuropsychopharmacology, 2020, 45(13), 2289-2298.
[http://dx.doi.org/10.1038/s41386-020-0772-2] [PMID: 32688367]
[27]
Xu, N.Z.; Ernst, M.; Treven, M.; Cerne, R.; Wakulchik, M.; Li, X.; Jones, T.M.; Gleason, S.D.; Morrow, D.; Schkeryantz, J.M.; Rahman, M.T.; Li, G.; Poe, M.M.; Cook, J.M.; Witkin, J.M. Negative allosteric modulation of alpha 5-containing GABAA receptors engenders antidepressant-like effects and selectively prevents age-associated hyperactivity in tau-depositing mice. Psychopharmacology (Berl.), 2018, 235(4), 1151-1161.
[http://dx.doi.org/10.1007/s00213-018-4832-9] [PMID: 29374303]
[28]
Matsumoto, K.; Puia, G.; Dong, E.; Pinna, G. GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders. Stress, 2007, 10(1), 3-12.
[http://dx.doi.org/10.1080/10253890701200997] [PMID: 17454962]
[29]
Zanos, P.; Thompson, S.M.; Duman, R.S.; Zarate, C.A., Jr; Gould, T.D. Convergent mechanisms underlying rapid antidepressant action. CNS Drugs, 2018, 32(3), 197-227.
[http://dx.doi.org/10.1007/s40263-018-0492-x] [PMID: 29516301]
[30]
Trullas, R.; Skolnick, P. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur. J. Pharmacol., 1990, 185(1), 1-10.
[http://dx.doi.org/10.1016/0014-2999(90)90204-J] [PMID: 2171955]
[31]
Ghasemi, M.; Montaser-Kouhsari, L.; Shafaroodi, H.; Nezami, B.G.; Ebrahimi, F.; Dehpour, A.R. NMDA receptor/nitrergic system blockage augments antidepressant-like effects of paroxetine in the mouse forced swimming test. Psychopharmacology (Berl.), 2009, 206(2), 325-333.
[http://dx.doi.org/10.1007/s00213-009-1609-1] [PMID: 19609507]
[32]
Maj, J.; Rogóz, Z.; Skuza, G.; Sowińska, H. Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. Eur. Neuropsychopharmacol., 1992, 2(1), 37-41.
[http://dx.doi.org/10.1016/0924-977X(92)90034-6] [PMID: 1638172]
[33]
Rogóz, Z.; Skuza, G.; Maj, J.; Danysz, W. Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats. Neuropharmacology, 2002, 42(8), 1024-1030.
[http://dx.doi.org/10.1016/S0028-3908(02)00055-2] [PMID: 12128003]
[34]
Corda, M.G.; Orlandi, M.; Lecca, D.; Giorgi, O. Decrease in GABAergic function induced by pentylenetetrazol kindling in rats: Antagonism by MK-801. J. Pharmacol. Exp. Ther., 1992, 262(2), 792-800.
[PMID: 1323663]
[35]
CzlConkowska, AI.; KrzaÎsacika, PC.; Sienkiewicz-Jaroszb, H.; Siemialtkowskib, M.; Szyndlera, J.; Bidzinaskic, A.; Plaznik, A. The effects of neurosteroids on picrotoxin-, bicuculline- and NMDA-induced seizures, and a hypnotic effect of ethanol. Pharmacol. Biochem. Behav., 2000, 67, 345-353.
[http://dx.doi.org/10.1016/S0091-3057(00)00369-5]
[36]
Giorgi, O.; Orlandi, M.; Lecca, D.; Corda, M.G. MK-801 prevents chemical kindling induced by pentylenetetrazol in rats. Eur. J. Pharmacol., 1991, 193(3), 363-365.
[http://dx.doi.org/10.1016/0014-2999(91)90152-G] [PMID: 1647322]
[37]
Naspolini, A.P.; Cocco, A.R.; Villa Martignoni, F.; Oliveira, M.S.; Furian, A.F.; Rambo, L.M.; Rubin, M.A.; Barron, S.; Mello, C.F. Traxoprodil decreases pentylenetetrazol-induced seizures. Epilepsy Res., 2012, 100(1-2), 12-19.
[http://dx.doi.org/10.1016/j.eplepsyres.2012.01.002] [PMID: 22281061]
[38]
Stephens, D.N.; Weidmann, R. Blockade of FG 7142 kindling by anticonvulsants acting at sites distant from the benzodiazepine receptor. Brain Res., 1989, 492(1-2), 89-98.
[http://dx.doi.org/10.1016/0006-8993(89)90892-5] [PMID: 2546658]
[39]
Sierra-Paredes, G.; Galán-Valiente, J.; Vazquez-Illanes, M.D.; Aguilar-Veiga, E.; Sierra-Marcuño, G. Effect of ionotropic glutamate receptors antagonists on the modifications in extracellular glutamate and aspartate levels during picrotoxin seizures: A microdialysis study in freely moving rats. Neurochem. Int., 2000, 37(4), 377-386.
[http://dx.doi.org/10.1016/S0197-0186(00)00038-3] [PMID: 10825578]
[40]
Schilling, M.; Wetzel, W.; Grecksch, G.; Becker, A. Pentylenetetrazole kindling affects sleep in rats. Epilepsia, 2006, 47(12), 2075-2082.
[http://dx.doi.org/10.1111/j.1528-1167.2006.00854.x] [PMID: 17201706]
[41]
Velísková, J.; Velísek, L.S. Picrotoxin-induced tonic-clonic seizures and lethality are decreased by MK-801 in developing rats. Pharmacol. Biochem. Behav., 1992, 43(1), 291-295.
[http://dx.doi.org/10.1016/0091-3057(92)90670-B] [PMID: 1409814]
[42]
Porsolt, R.D.; Anton, G.; Blavet, N.; Jalfre, M. Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur. J. Pharmacol., 1978, 47(4), 379-391.
[http://dx.doi.org/10.1016/0014-2999(78)90118-8] [PMID: 204499]

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