Enhancement of N-methyl-D-aspartate receptor-mediated excitatory postsynaptic potentials in the neostriatum after methamphetamine sensitization

Abstract

It has been suggested that behavioral methamphetamine sensitization involves changes in cortical excitatory synaptic inputs to neostriatal (Str) projection neurons. To test this, we performed blind whole-cell recording of medium spiny neurons in Str slice preparations. In Str neurons of naive rats, the amplitude of the subcortical white matter stimulation-induced N-methyl- D-aspartate receptor-mediated excitatory postsynaptic potentials (NMDA-EPSPs) was decreased upon hyperpolarization, owing to the voltage-dependent Mg(2+) blockade of NMDA receptor channels. In contrast, the amplitude of the NMDA-EPSPs in Str neurons of rats undergoing methamphetamine withdrawal (MW) did not show the Mg(2+) blockade and was nearly voltage independent over the membrane potential range of -70 to -110 mV. Application of the specific protein kinase C (PKC) activator, phorbol 12, 13- DL-acetate, blocked the voltage-dependent Mg(2+) blockade of NMDA receptor channels in Str neurons of naive rats. Application of the specific activator of cAMP-dependent protein kinase A (PKA), Sp-cAMPS-triethylamine salt, increased the amplitude of the NMDA receptor-mediated EPSPs at the rest but not at hyperpolarized potentials. Coapplication of the PKC and PKA activators yielded NMDA-EPSPs similar to those seen in Str neurons of MW rats. In Str slices of naive rats, tetanic subcortical white matter stimulation induced long-term depression of field potentials. In Str slices treated with the PKC and/or PKA, the same stimulation induced long-term potentiation of field potentials similar to those observed in slices obtained from MW rats. These results suggest that the enhancement of the NMDA receptor-mediated corticostriatal synaptic transmission plays an important role in behavioral methamphetamine sensitization. This enhancement is probably associated with phosphorylation of NMDA receptors mediated by the simultaneous activation of PKC and PKA.

Potentiation of N-methyl-d-aspartate receptor-mediated neuronal injury during methamphetamine withdrawal in vitro requires co-activation of IP3 receptors

“…However, longterm withdrawal (7 days) did result in a markedly potentiated neurotoxic response to NMDA exposure, a finding that is consistent with the electrophysiological findings of Moriguchi et al (2002). Long-term withdrawal does appear to be an essential component of the observed neurotoxicity, since short-term withdrawal and chronic exposure without withdrawal did not result in a potentiated NMDA effect.…”

“…Long-term NMDA receptor antagonism by METH may result in neuronal excitability during withdrawal. In fact, Moriguchi et al (2002) reported increased amplitudes of NMDA mediated excitatory postsynaptic potentials (EPSPs) in neostriatal slices following withdrawal from METH. Evidence of neuronal excitability during protracted METH withdrawal suggests that compensatory responses to chronic METH administration may be similar to other NMDA antagonists.…”

“…Previous literature has suggested that METH may directly or indirectly influence the NMDA receptor in a biphasic manner (Moriguchi et al, 2002;Smith et al, 2007;Yeh et al, 2002). Short-term, repeated administration of METH to rodents has been shown to increase hippocampal and striatal glutamate content (Mark et al 2007;Rocher and Gardier, 2001) while long-term METH administration was shown to deplete hippocampal glutamate content (Kaiya et al 1982).…”

“…It has become increasingly evident that N-Methyl-D-Aspartate-type glutamate receptors are targets of METH actions (Moriguchi et al, 2002;Smith et al, 2007;Yeh et al, 2002). Previous literature has suggested that METH may directly or indirectly influence the NMDA receptor in a biphasic manner (Moriguchi et al, 2002;Smith et al, 2007;Yeh et al, 2002).…”

“…desensitization, after Krupp et al 1996), suggest that long-term METH exposure may result in adaptive changes of NMDA receptor abundance or function during withdrawal. In fact, Moriguchi et al (2002) have reported that long-term METH exposure followed by long-term withdrawal may reduce Mg 2+ blockade of the NMDA receptor resulting in increased EPSPs.…”