Lack of long-term changes in cocaine and monoamine concentrations in rat CNS following chronic administration of cocaine.
In previous studies, we reported time-dependent and dose-dependent changes in the rat dopaminergic receptor system following chronic administration of cocaine. The aim of the present investigation was to monitor the concentration of monoamines (using HPLC-ECD) and cocaine (using GC-PCI/MS) in rat CNS following a dose schedule of 5, 10, 15, 20 and 25 mg/kg, i.p., b.i.d. for 21 days. 12 h after the last cocaine injection, cortical and striatal concentrations of monoamines and their metabolites were not significantly different in saline vs cocaine treated animals. In addition, the cocaine concentration in the brain regions examined did not change with the different doses used. Accumulation of a metabolite of cocaine (ecgonine methyl ester) was the only alteration found. These results indicate that alterations in the dopaminergic receptor system following chronic cocaine administration are not due to changes in neurotransmitter concentration or accumulation of cocaine in the brain.
Alburges
M E
ME
Pharmacology and Toxicology Department, University of Utah, Salt Lake City 84108, USA.
Crouch
D J
DJ
Andrenyak
D M
DM
Wamsley
J K
JK
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004563:Electrochemistry; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine