Effects of mood stabilizers on the disruption of prepulse inhibition induced by apomorphine or dizocilpine in mice.
The prepulse inhibition of the startle response provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. Prepulse inhibition deficits were observed in patients with several neuropsychiatric disorders, including schizophrenia and acute manic bipolar patients. Valproic acid, carbamazepine and lithium carbonate are frequently used as mood stabilizers in patients with bipolar affective disorder and schizophrenia. However, little is known about the mechanisms of action of mood stabilizers on prepulse inhibition deficits. In this study, we investigated the effects of mood stabilizers on the disruption of prepulse inhibition of the acoustic startle response induced by either apomorphine or dizocilpine in mice. Valproate (30-300 mg/kg, i.p.), carbamazepine (3-30 mg/kg, i.p.) and lithium carbonate (10-100 mg/kg, p.o.) had any effect on prepulse inhibition by itself. Valproate, carbamazepine and lithium carbonate reversed the disruption of prepulse inhibition induced by apomorphine (1 mg/kg, s.c.). Although valproate and carbamazepine had no effect on the disruption of prepulse inhibition induced by dizocilpine (0.3 mg/kg, s.c.), lithium carbonate exacerbated the dizocilpine-induced disruption. These results suggest that valproate, carbamazepine and lithium carbonate reverse the disruption of prepulse inhibition through the dopaminergic system.
Umeda
Kenta
K
Department of Neuropharmacology Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Suemaru
Katsuya
K
Todo
Nobuko
N
Egashira
Nobuaki
N
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
Araki
Hiroaki
H
D000339:Affect / Q000187:drug effects*; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001058:Apomorphine / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018682:GABA Agents / Q000494:pharmacology; D016651:Lithium Carbonate / Q000494:pharmacology; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology
D018692:Antimanic Agents; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D018682:GABA Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016651:Lithium Carbonate; D002220:Carbamazepine; D014635:Valproic Acid; D016291:Dizocilpine Maleate; D001058:Apomorphine