ALTERATIONS IN STRIATAL ZIF 268, PREPRODYNORPHIN AND PREPROENKEPHALINMESSENGER-RNA EXPRESSION INDUCED BY REPEATED AMPHETAMINE ADMINISTRATION IN RATS/

Quantitative in situ hybridization histochemistry was used to compare the effects of AMPH administration on mRNAs coding for zif/268, a memb er of the zinc finger family of immediate early genes, and the opioid peptides, preprodynorphin (PPD) and preproenkephalin (PPE), in rat str iatum after 3 dosing schedules: (1) acute; (2) once a day for 5 days, and (3) once a day for 5 days followed 10 days later by a challenge do se. Behavioral ratings indicated that the activity of rats was signifi cantly higher after 5 daily AMPH (5 mg/kg, i.p.) injections than after a single 5 mg/kg injection and that the activity of AMPH-pretreated r ats was significantly higher than that of saline-pretreated rats after a 1 mg/kg challenge dose 10 days later. Three hours after acute admin istration of AMPH to naive rats, PPD mRNA expression in the dorsal (ca udatoputamen) and ventral (nucleus accumbens, NAc) striatum as well as PPE and zif/268 mRNA expression in the dorsal, but not ventral, stria tum were increased as compared to saline-treated rats. Five daily trea tments with AMPH augmented acute AMPH-induced increases in PPD mRNA ex pression in the caudatoputamen but not in the NAc. The increase in str iatal zif/268 mRNA expression induced by acute AMPH was, in contrast, reduced after 5 daily treatments with AMPH. AMPH induced PPE expressio n to the same extent in rats treated with one or 5 daily injections. H ybridization performed 3 h after AMPH challenge in AMPH-pretreated rat s failed to demonstrate augmentation of AMPH-stimulated zif/268, PPD, or PPE mRNA expression in the striatum as compared to saline-pretreate d rats. These results indicate that an augmented response of PPD and a decreased response of zif/268 mRNA expression in striatal neurons are closely associated with the initiation of behavioral sensitization in duced by repeated, intermittent AMPH treatments. In contrast, a clear dissociation exists between the expression of sensitized behaviors and unsensitized zif/268, PPD and PPE mRNA in the striatum in response to a challenge dose of AMPH. Possible functional implications of these a lterations in the initiation and expression of AMPH-induced behavioral sensitization are discussed.