Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801)

Abstract

These results suggest the involvement of increased glutamate levels and an activation of PKC in delayed-induced synaptic and cellular plasticity underlying the higher dose of METH-induced behavioral sensitization to dizocilpine.

Differential modulation of methamphetamine-mediated behavioral sensitization by overexpression of Mu opioid receptors in nucleus accumbens and ventral tegmental area

“…Several studies have indicated that glutamate is involved in Meth behavioral sensitization (Fang et al 2005;Vanderschuren and Kalivas 2000). We recently reported that Meth induces a rapid increase in Ca ++ influx in neuronal cells overexpressing gCaMP5, an intracellular Ca ++ probe.…”

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

“…Our group recently found that treatment with a PKC inhibitor, staurosporine, 120 min after high-dose METH injection (2.5 mg/kg) blocked METH-induced crosssensitization to MK-801, but not sensitization to METH (Fang et al 2005). Chronic administration of VPA decreases PKC activity and levels of the PKC alpha and epsilon subunits (Chen et al 1994).…”

“…As discussed previously (Ito et al 2004;Fang et al 2005), this higher dose of METH (2.5 mg/kg) delays increases in Glu levels and may induce neuroplastic changes that are related to cross-sensitization to MK-801. Taking these findings into account, the present study hypothesized that posttreatment with VPA would inhibit the METH-induced delayed increases in Glu levels in the NAC; this inhibition would block high-dose METH-induced cross-sensitization to MK-801.…”

“…Our group (Fang et al 2005) recently showed that a protein kinase C (PKC) inhibitor, staurosporine, blocked the induction of high-dose METH-induced behavioral cross-sensitization to an NMDA receptor antagonist, MK-801, but not METH, and postulated that activation of PKC is related to METHinduced delayed increases in Glu in the NAC and the development of the cross-sensitization to MK-801.…”

“…Based on the fact that 2.5 mg/kg METH induced delayed increases in basal levels of Glu in the NAC, we administered VPA at 120 min after METH injection to block the phenomena related to delayed increases in Glu levels. These time courses were based on analogous studies carried out by our group (Abekawa et al 2002a,b;Fang et al 2005).…”