FOCAL AND SYSTEMIC COCAINE DIFFERENTIALLY AFFECT EXTRACELLULAR NOREPINEPHRINE IN THE LOCUS-COERULEUS, FRONTAL-CORTEX AND HIPPOCAMPUS OF THEANESTHETIZED RAT

The purpose of this study was to characterize and compare the effects of cocaine on norepinephrine (NE) overflow in the forebrain and somato dendritic regions of anaesthetized rats with microdialysis. Intraperit oneal injections of cocaine (20 mg/kg) failed to increase NE overflow in the hippocampus and the frontal cortex but did elevate NE in the re gion of the locus coeruleus. Focal application of cocaine (1-100 mu M) via the dialysis probe into the region of the locus coeruleus also pr oduced a concentration dependent elevation of extracellular NE. In the terminal regions the application of focal cocaine (1-100 mu M) showed a differential effect, with a concentration dependent increase in ext racellular NE in the hippocampus, whilst in the frontal cortex only th e highest concentration of cocaine (100 mu M) elevated extracellular N E. The regional differences seen following focal applications in this study may be related to differences in transporter function in the thr ee brain areas or to differences in the affinity for cocaine. The inab ility of systemically administered cocaine to increase hippocampal and cortical NE is probably related to its predominant actions in the som atodendritic region.