Effects of high dosage methamphetamine on glutamatergic neurotransmission in the nucleus accumbens and prefrontal cortex.

Abstract

RationaleMethamphetamine (METH) induces changes in the glutamatergic system and elicits cellular alterations in the cortico-accumbens circuit. ObjectiveWhile there is a body of literature on the effects of METH on dopaminergic transmission, there is a gap in knowledge regarding the effects of a high dose of METH on synaptic glutamatergic neurotransmission, specifically in brain regions involved in goal directed behavior (nucleus accumbens core; NAc core) and executive functions (prefrontal cortex;PFC). MethodsIn order to fill that gap we assessed synaptic glutamatergic transmission using a well established METH administration regime (4 x 4 mg/kg ip at 2 hr intervals) followed by 7 days of abstinence. Rats were then sacrificed and whole cell and field recordings were performed in the NAc core and medial PFC. ResultsMETH treatment elicited a significant decrease in paired pulse ratio in NAc core and a significant increase in AMPA/NMDA ratio driven by increases in AMPA currents. On the other hand, there were no significant changes in measures of synaptic glutamate in the PFC. ConclusionThese results suggest that a high dose of METH treatment followed by a period of abstinence elicits significant increases in indices of glutamatergic transmission in the NAc core with no detectable changes in mPFC, denoting that neurons and glutamate terminals in this limbic region have a higher susceptibility to a neurotoxic METH regime.