Focal and systemic cocaine differentially affect extracellular norepinephrine in the locus coeruleus, frontal cortex and hippocampus of the anaesthetized rat.
The purpose of this study was to characterize and compare the effects of cocaine on norepinephrine (NE) overflow in the forebrain and somatodendritic regions of anaesthetized rats with microdialysis. Intraperitoneal injections of cocaine (20 mg/kg) failed to increase NE overflow in the hippocampus and the frontal cortex but did elevate NE in the region of the locus coeruleus. Focal application of cocaine (1-100 microM) via the dialysis probe into the region of the locus coeruleus also produced a concentration dependent elevation of extracellular NE. In the terminal regions the application of focal cocaine (1-100 microM) showed a differential effect, with a concentration dependent increase in extracellular NE in the hippocampus, whilst in the frontal cortex only the highest concentration of cocaine (100 microM) elevated extracellular NE. The regional differences seen following focal applications in this study may be related to differences in transporter function in the three brain areas or to differences in the affinity for cocaine. The inability of systematically administered cocaine to increase hippocampal and cortical NE is probably related to its predominant actions in the somatodendritic region.
Thomas
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Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
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D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
D003042:Cocaine; D009638:Norepinephrine