ACUTE METHAMPHETAMINE-INDUCED ZIF 268, PREPRODYNORPHIN, AND PREPROENKEPHALIN MESSENGER-RNA EXPRESSION IN RAT STRIATUM DEPENDS ON ACTIVATIONOF NMDA AND KAINATE/AMPA RECEPTORS/

This study tested the role of N-methyl-D-aspartate and kainate/AMPA re ceptors in mediating mRNA expression of the immediate early gene zif/2 68 and the opioid peptide genes preprodynorphin and preproenkephalin i n rat forebrain following a single injection of methamphetamine. At 3 h after acute methamphetamine [4 mg/kg, intraperitoneally (IP)], quant itative in situ hybridization histochemistry revealed that zif/268 mRN A expression was increased in the dorsal striatum (caudoputamen) and i n the sensory cortex. Preprodynorphin was increased in both dorsal and ventral striatum (nucleus accumbens) and preproenkephalin was increas ed in the dorsal striatum. Pretreatment with -)-3-(2-carboxypiperazin- 4-yl)-propyl-1-phosphonic acid (CPP) (10 mg/kg, IP), an N-methyl-D-asp artate receptor antagonist, blocked the methamphetamine-induced zif/26 8 mRNA expression in the striatum and in the region of sensory cortex representing the upper limb and nose. 6,7-Dinitro-quinoxaline-2,3-dion e (DNQX) (100 mg/kg, IP), a kainate/AMPA receptor antagonist, did not reduce the ability of methamphetamine to induce zif/268 mRNA in striat al and cortical neurons. Furthermore, both antagonists caused a parall el blockade of methamphetamine-stimulated preprodynorphin mRNA express ion in the dorsal and ventral striatum but did not significantly affec t methamphetamine-stimulated preproenkephalin mRNA expression. CPP and DNQX reduced basal levels of zif/268 mRNA in cortical and striatal ne urons but did not affect the constitutive expression of the two opioid mRNAs in the striatum. Neither antagonist had a significant effect on methamphetamine-induced hyperlocomotion and stereotypies. These resul ts demonstrate that both N-methyl-D-aspartate and kainate/AMPA recepto r-mediated glutamatergic transmission is linked to modulation of the m ethamphetamine-stimulated opioid peptide gene expression in rat forebr ain. Furthermore, N-methyl-D-aspartate receptors participate in metham phetamine-stimulated zif/268 expression.