THE EFFECTS OF METHAMPHETAMINE AND COCAINE ON MOTOR BEHAVIOR AND EXTRACELLULAR DOPAMINE IN THE VENTRAL STRIATUM OF LEWIS VERSUS FISCHER-344RATS

The effects of an acute systemic injection of methamphetamine (m4MP) o r cocaine (COG) on motor behavior (stereotypy, locomotor activity, and rearing) and extracellular dopamine (DA) in the ventral striatum were compared in Lewis (LEW) versus Fischer 344 (F344) rats, using in vivo microdialysis in awake freely moving animals. In addition, the behavi oral response to repeated mAMP injections (i.e. sensitization) was cha racterized in LEW and F344 rats, as was the possibility of strain diff erences in drug pharmacokinetics. The major findings were: (i) LEW rat s showed greater behavioral activation to an acute injection of both m AMP and COG, as indicated by a shift to the left in the dose-effect cu rves relative to F344 rats. (ii) LEW rats were more susceptible to mAM P sensitization. (iii) An acute injection of mAMP or COC enhanced the extracellular concentration of DA to a greater extent in LEW rats, as indicated by a significant shift to the left in the dose-effect curve relative to F344 rats. (iv) Strain differences in the behavioral and n eurochemical effects of these drugs were characterized largely by diff erences in the duration of the drug response. (v) LEW rats had higher plasma and brain levers of mAMP and COC than F344 rats, suggesting tha t strain differences in pharmacokinetics may contribute to strain diff erences in the behavioral and neurochemical effects of these drugs.