Lamotrigine blocks apoptosis induced by repeated administration of high-dose methamphetamine in the medial prefrontal cortex of rats

• Published in: Neuroscience letters 2011-03, Vol.490 (3), p.161-164
• Main Authors: Nakato, Yasuya, Abekawa, Tomohiro, Ito, Koki, Inoue, Takeshi, Koyama, Tsukasa
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Anticonvulsants - pharmacology; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Central Nervous System Stimulants - administration & dosage; Drug Administration Schedule; Drug Interactions; Fundamental and applied biological sciences. Psychology; Glutamate; Glutamic Acid - metabolism; In Situ Nick-End Labeling - methods; Lamotrigine; Male; Medical sciences; Methamphetamine; Methamphetamine - administration & dosage; Prefrontal Cortex - drug effects; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Sprague-Dawley; Schizophrenia; Triazines - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.11.028

▶ Apoptosis plays an important role in progressive cortical atrophy in schizophrenia. ▶ Methamphetamine (METH) induced apoptosis in the medial prefrontal cortex (mPFC). ▶ METH increased extracellular glutamate levels in the mPFC. ▶ Lamotrigine (LTG) prevented these changes induced by METH in the mPFC. ▶ LTG may prevent longitudinal pathophysiological development in schizophrenia. 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 (30mg/kg) on methamphetamine (METH, 2.5mg/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 (30mg/kg) on repeated METH (2.5mg/kg)-induced apoptosis in this region of rats was investigated. Results show that LTG (30mg/kg) blocked the METH (2.5mg/kg)-induced glutamate increase in the mPFC. Repeated co-administration of LTG (30mg/kg) blocked the development of apoptosis induced by repeated administration of METH (2.5mg/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.