ROLE OF KAINATE AMPA RECEPTORS IN INDUCTION OF STRIATAL ZIF/268 AND PREPRODYNORPHIN MESSENGER-RNA BY A SINGLE INJECTION OF AMPHETAMINE/

The role of kainate/AMPA excitatory amino acid receptors in D-amphetam ine (AMPH)-induced behavioral changes and the induction of immediate e arly gene and preprodynorphin (PPD) mRNA in various regions of rat for ebrain was investigated with quantitative in situ hybridization histoc hemistry. 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 in creased in the sensorimotor cortex. Pretreatment of rats with DNQX, a kainate/AMPA receptor antagonist, did not affect the behaviors elicite d by AMPH. However, the AMPH-stimulated increase in PPD and zif/268 mR NA levels in striatum, but not zif/268 mRNA in cortex, was blocked by DNQX pretreatment. In contrast, DNQX alone attenuated basal (constitut ive) levels of zif/268 mRNA expression in sensorimotor cortical, but n ot in striatal, neurons. These studies indicate that kainate/AMPA rece ptors mediate the induction of zif/268 and PPD mRNA expression in the caudate nucleus induced by a single injection of AMPH. The fact that D NQX blocked genomic, but not behavioral, responses to acute AMPH sugge sts 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 pl ay a key role in maintaining constitutive expression of the zif/268 ge ne in cortical neurons.