Lamotrigine prevents ketamine but not amphetamine-induced deficits in prepulse inhibition in mice.
BACKGROUND
Lamotrigine, a broad-spectrum anticonvulsant known to block brain sodium channels, is effective in the treatment of persons with bipolar disorder, perhaps by virtue of its ability to reduce glutamate release. Furthermore, lamotrigine decreases the perceptual abnormalities produced by the N-methyl- d-aspartate (NMDA) antagonist ketamine in humans, similar to the effects of the atypical antipsychotic clozapine. Acutely manic bipolar patients, like persons with schizophrenia, Tourette's, and obsessive compulsive disorder, exhibit decreases in sensorimotor gating, as measured by prepulse inhibition of the startle response (PPI).


OBJECTIVE
We assessed the ability of lamotrigine to reduce the PPI-disruptive effects of ketamine and the dopaminergic agent amphetamine in two inbred mouse strains, C57BL/6J and 129SvPasIco.


METHODS
Mice were tested in a standard PPI paradigm after administration of lamotrigine (0, 6.7, 13, or 27 mg/kg) or a combination of lamotrigine (27 mg/kg) and either d-amphetamine (10 mg/kg) or ketamine (100 mg/kg).


RESULTS
In the 129SvPasIco mice, lamotrigine reversed the ketamine-induced PPI deficit, without altering PPI in control mice. In C57BL/6J mice, however, 27 mg/kg lamotrigine generally increased PPI in both control and ketamine-treated mice. Lamotrigine did not ameliorate the amphetamine-induced PPI deficit in either strain.


CONCLUSIONS
In conclusion, lamotrigine can increase PPI on its own and prevent ketamine-induced, but not amphetamine-induced, disruptions of PPI. These results suggest that lamotrigine may exert its effects on PPI through the glutamatergic system.
Brody
Suzanne A
SA
Department of Psychiatry and Neurosciences, University of California, 9500 Gilman Drive, La Jolla, San Diego, CA 92093-0804, USA.
Geyer
Mark A
MA
Large
Charles H
CH
D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007649:Ketamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077213:Lamotrigine; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009433:Neural Inhibition / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects; D013045:Species Specificity; D014227:Triazines / Q000494:pharmacology*
D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D014227:Triazines; D007649:Ketamine; D000661:Amphetamine; D000077213:Lamotrigine