Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala:: implications for its effects in seizure and affective disorders

被引:56
作者
Braga, MFM
Aroniadou-Anderjaska, V
Post, RM
Li, H
机构
[1] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA
[2] NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA
关键词
lamotrigine; amygdala; GABA(A); inhibition; affective disorders; bipolar depression;
D O I
10.1016/S0028-3908(01)00198-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lamotrigine (LTG) is an antiepileptic drug that is also effective in the treatment of certain psychiatric disorders. Its anticonvulsant action has been attributed to its ability to block voltage-gated Na+ channels and reduce glutamate release. LTG also affects GABA-mediated synaptic transmission, but there are conflicting reports as to whether inhibitory transmission is enhanced or suppressed by LTG. We examined the effects of LTG on GABA(A), receptor-mediated synaptic transmission in slices from rat amygdala, it brain area that is particularly important in epileptogenesis and affective disorders. In intracellular recordings, LTG (100 muM) reduced GABA(A), reccptor-mediated IPSPs evoked by electrical stimulation in neurons of the basolateral nucleus. In whole-cell recordings LTG (10.50 and 100 muM) decreased the frequency and amplitude of spontaneous IPSCs, as well as the amplitude of evoked IPSCs, but had no effect on the kinetics of these Currents. LTG also had no effects on the frequency, amplitude or kinetics of miniature IPSCs recorded in the presence of TTX. These results suggest that in the basolateral amygdala. LTG Suppresses GABA(A) receptor-mediated synaptic transmission by a direct and/or indirect effect oil presynaptic Ca++ influx. The modulation of inhibitory synaptic transmission may be an important mechanism Underlying the psychotropic effects of LTG. Published by Elsevier Science Ltd.
引用
收藏
页码:522 / 529
页数:8
相关论文
共 40 条
[1]  
Aggleton J.P., 2000, AMYGDALA FUNCTIONAL, V2nd
[2]   Input-specific LTP and depotentiation in the basolateral amygdala [J].
Aroniadou-Anderjaska, V ;
Post, RM ;
Rogawski, MA ;
Li, H .
NEUROREPORT, 2001, 12 (03) :635-640
[3]   Unitary synaptic currents between lacunosum-moleculare interneurones and pyramidal cells in rat hippocampus [J].
Bertrand, S ;
Lacaille, JC .
JOURNAL OF PHYSIOLOGY-LONDON, 2001, 532 (02) :369-384
[4]   A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder [J].
Calabrese, JR ;
Suppes, T ;
Bowden, CL ;
Sachs, GS ;
Swann, AC ;
McElroy, SL ;
Kusumakar, V ;
Ascher, JA ;
Earl, NL ;
Greene, PL ;
Monaghan, ET .
JOURNAL OF CLINICAL PSYCHIATRY, 2000, 61 (11) :841-850
[5]   An in vitro electrophysiological study on the effects of phenytoin, lamotrigine and gabapentin on striatal neurons [J].
Calabresi, P ;
Centonze, D ;
Marfia, GA ;
Pisani, A ;
Bernardi, G .
BRITISH JOURNAL OF PHARMACOLOGY, 1999, 126 (03) :689-696
[6]  
CHEUNG H, 1992, EPILEPSY RES, V13, P107
[7]   The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro [J].
Cunningham, MO ;
Jones, RSG .
NEUROPHARMACOLOGY, 2000, 39 (11) :2139-2146
[8]   Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: Quantal fluctuation affects subsequent release [J].
Debanne, D ;
Guerineau, NC ;
Gahwiler, BH ;
Thompson, SM .
JOURNAL OF PHYSIOLOGY-LONDON, 1996, 491 (01) :163-176
[9]   Clozapine plus lamotrigine in treatment-resistant schizophrenia [J].
Dursun, SM ;
McIntosh, D .
ARCHIVES OF GENERAL PSYCHIATRY, 1999, 56 (10) :950-950
[10]  
Engle PM, 2000, ANN PHARMACOTHER, V34, P258