Role of kainate/AMPA receptors in induction of striatal zif/268 and preprodynorphin mRNA by a single injection of amphetamine.

The role of kainate/AMPA excitatory amino acid receptors in D-amphetamine (AMPH)-induced behavioral changes and the induction of immediate early gene and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), PPD mRNA and mRNA of the transcription factor zif/268, but not c-fos, was increased in dorsal striatum (caudate). Zif/268 mRNA was also increased in the sensorimotor cortex. Pretreatment of rats with DNQX, a kainate/AMPA receptor antagonist, did not affect the behaviors elicited by AMPH. However, the AMPH-stimulated increase in PPD and zif/268 mRNA levels in striatum, but not zif/268 mRNA in cortex, was blocked by DNQX pretreatment. In contrast, DNQX alone attenuated basal (constitutive) levels of zif/268 mRNA expression in sensorimotor cortical, but not in striatal, neurons. These studies indicate that kainate/AMPA receptors mediate the induction of zif/268 and PPD mRNA expression in the caudate nucleus induced by a single injection of AMPH. The fact that DNQX blocked genomic, but not behavioral, responses to acute AMPH suggests that kainate/AMPA receptor mechanisms may be involved in the long-term (possibly sensitizing) effects, rather than the acute effects, of the drug. In addition, tonic kainate/AMPA receptor stimulation may play a key role in maintaining constitutive expression of the zif/268 gene in cortical neurons.