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

Abstract

3

Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats

“…The respective vehicles for METH and LTG were saline (1 ml/kg) and approximately 0.002 N HCl in distilled water (4 ml/kg). This study used dosages of METH (2.5 mg/kg) and LTG (30 mg/kg) that were chosen after considering the results obtained from previous studies [15,16].…”

“…In an animal model, LTG plus clozapine decreased hyperlocomotion induced by the NMDA receptor antagonist phencyclidine in rats [25]. Our recent report described that prepulse inhibition deficit and the increase of TUNEL-positive cells in the mPFC induced by repeated administration of 2.5 mg/kg of METH are prevented by repeated co-administration of LTG [15,16]. Moreover, our group presented data showing that LTG inhibits increased extracellular glutamate levels in the mPFC induced by 2.5 mg/kg of METH [16].…”

“…We postulated that changes in glutamatergic neural transmission induced by psychostimulants such as methamphetamine (METH) and amphetamine are closely related to this sensitization [1,2,10,16].…”

“…That dosage, but not 1.0 mg/kg (which increases extracellular dopamine levels but not glutamate levels), can increase both extracellular glutamate and dopamine levels in the medial prefrontal cortex (mPFC) [1,2]. It induces schizophrenia-related behavioral and histological abnormalities including cross-sensitization to the NMDA receptor antagonist, a neuroplastic prepulse inhibition (PPI) deficit, and an apoptotic reaction in the mPFC [1,2,10,11,15,16].…”

“…The METH 2.5 mg/kg induced a delayed increase in the basal levels of glutamate in the mPFC [1,2,16]. Therefore, we administered LTG 120 min after METH injection to block phenomena related to the delayed increase in glutamate levels.…”