Valproate blocks high-dose methamphetamine-induced behavioral cross-sensitization to locomotion-inducing effect of dizocilpine (MK-801), but not methamphetamine

Section: Discussionmentioning

confidence: 99%

“…Our group has demonstrated that a single administration of METH, at 2.5 mg/kg, increases the extracellular glutamate levels in the mPFC [2] and the nucleus accumbens (NAC) [13,14]. Furthermore, repeated administration of METH (2.5 mg/kg) induces apoptosis in the mPFC.…”

Section: Introductionmentioning

confidence: 99%

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

Nakato

Abekawa

Ito

et al. 2011

“…Our previous study revealed that 2.5 mg/kg, but not 1.0 mg/kg of METH induced increases in glutamate levels in the mPFC [1] and the nucleus accumbens [14,15], suggesting that repeatedly increased glutamate release in the neuronal circuit, which comprises the mPFC and nucleus accumbens, is related to the METH-induced long-lasting PPI deficit. Furthermore our group [1] found that several drugs such as olanzapine and risperidone, which block METH-induced delayed increase in extracellular glutamate levels in mPFC, prevented the initiation of PPI deficit induced by the repeated administration of METH.…”

Section: Discussionmentioning

confidence: 91%

“…Therefore, expression of the neuroplastic PPI deficit induced by the repeated administration of METH might reflect the state underlying hypofunction of NMDA receptors [15]. The PPI deficit is induced acutely by hypofunction of NMDA receptor-mediated glutamatergic neurotransmission by a single administration of NMDA receptor antagonists [4].…”

Section: Discussionmentioning

confidence: 99%

Lamotrigine blocks the initiation and expression of repeated high-dose methamphetamine-induced prepulse inhibition deficit in rats

Nakato¹,

Abekawa²,

Ito³

et al. 2010

Our group developed a new psychostimulant animal model reflecting some clinical aspects of schizophrenia better than the conventional model does. In this model, long-lasting prepulse inhibition (PPI) deficit at the basement state is induced via repeated administration of methamphetamine (METH, 2.5 mg/kg) without challenge injection of this psychostimulant. This study elucidates the effects of lamotrigine (LTG, 30 mg/kg) on the initiation and expression of a steady-state PPI deficit induced by the repeated METH administration. We assessed the effect of coadministration of LTG and METH on the initiation of PPI deficit. The LTG was injected 120 min after each METH injection for 5 times on every alternate day and for an additional 5 times every day, amounting to a total of 10 times. After 11-13 days of the withdrawal period, we measured PPI using the SR-LAB system. Using other animals after 20 min of LTG injection, we subsequently examined the effect of a single injection of LTG on the expression of PPI deficit caused by the repeated METH administration.The LTG blocked the initiation of PPI deficit induced by the repeated METH administration at 68 dB of prepulse intensity, but had no effect on the startle amplitude. The LTG prevented the initiation and expression of neuroplastic PPI deficit detected at the baseline state without any METH challenge injection, which was induced by the repeated administration of this psychostimulant.Results suggest that LTG is useful for blocking progressive deterioration of neurocognitive function and recovering the neurocognitive deficit in schizophrenia.3

“…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].…”

Section: Introductionmentioning

confidence: 99%

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

Nakato

Abekawa

Inoue

et al. 2011