ACTIVATOR PROTEIN-1 BINDING ACTIVITIES IN DISCRETE REGIONS OF RAT-BRAIN AFTER ACUTE AND CHRONIC ADMINISTRATION OF METHAMPHETAMINE

The activator protein-1 (AP-1) binding activities increased in three b rain regions (striatum, nucleus accumbens, and cingulate cortex) after a single methamphetamine (METH) injection to rats. Pretreatment with SCH 23390, but not(-)-eticlopride, significantly inhibited the enhance d AP-1 binding activities induced by acute METH administration. The ma gnitude of enhancement of AP-I binding activities 3 h after the last d ose of chronic METH administration (4 mg/kg once daily for 14 days) wa s significantly attenuated as compared with those 3 h after a single M ETH administration. The AP-I binding activities after a 1- but not 4-, week abstinence from chronic administration of METH were still signif icantly higher than those of the saline-treated controls. A METH chall enge after a 4-week abstinence period induced significantly lower AP-1 binding activities in rats chronically injected with METH than in rat s chronically injected with saline, The supershift assay revealed that the levels of Jun family protein, but not Fos-related antigen, increa sed significantly in the striatum and nucleus accumbens of chronically METH-treated rats after a 1-week abstinence. These results suggest th at chronic METH administration leads to delayed decay of the induced A P-1 binding activities and Jun component levels after abstinence for u p to 1 week but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after ab stinence for 4 weeks.