Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: implications for its effects in seizure and affective disorders.
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, a brain area that is particularly important in epileptogenesis and affective disorders. In intracellular recordings, LTG (100 microM) reduced GABA(A) receptor-mediated IPSPs evoked by electrical stimulation in neurons of the basolateral nucleus. In whole-cell recordings, LTG (10, 50 and 100 microM) 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 on presynaptic Ca(++) influx. The modulation of inhibitory synaptic transmission may be an important mechanism underlying the psychotropic effects of LTG.
Braga
M F M
MF
Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland, MD 20814, USA.
Aroniadou-Anderjaska
V
V
Post
R M
RM
Li
H
H
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D000077213:Lamotrigine; D019964:Mood Disorders / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D014227:Triazines; D000077213:Lamotrigine