title: Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats.
abstract: Lamotrigine (LTG) is sometimes co-administered with antipsychotic drugs for the treatment of schizophrenia. Nevertheless, the pharmacological basis of LTG use for schizophrenia has not been reported. Our group recently proposed a new psychostimulant animal model that might reflect the progressive pathophysiology of schizophrenia. Results obtained using that model show that LTG blocks the initiation and expression of repeated high-dosage methamphetamine-induced prepulse inhibition deficit in rats (Nakato et al., 2010, Neurosci. Lett. [25]). Using the model, the effect of LTG (30 mg/kg) on methamphetamine (METH, 2.5 mg/kg)-induced increases in extracellular glutamate levels in the medial prefrontal cortex (mPFC) was examined in this study. Then the effect of repeated co-administration of LTG (30 mg/kg) on repeated METH (2.5 mg/kg)-induced apoptosis in this region of rats was investigated. Results show that LTG (30 mg/kg) blocked the METH (2.5 mg/kg)-induced glutamate increase in the mPFC. Repeated co-administration of LTG (30 mg/kg) blocked the development of apoptosis induced by repeated administration of METH (2.5 mg/kg) in the mPFC. The LTG blocks histological abnormalities induced by repeated administration of METH, which suggests a mechanism of LTG that protects against progressive pathophysiology in schizophrenia.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo, Hokkaido, Japan.
authors.forename: Yasuya
authors.initials: Y
authors.lastname: Nakato
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Abekawa
authors.forename: Koki
authors.initials: K
authors.lastname: Ito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018698:Glutamic Acid / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D000077213:Lamotrigine; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D017397:Prefrontal Cortex / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D014227:Triazines; D018698:Glutamic Acid; D008694:Methamphetamine; D000077213:Lamotrigine