Chronic treatment with a dopamine uptake blocker changes dopamine and acetylcholine but not glutamate and GABA concentrations in prefrontal cortex, striatum and nucleus accumbens of the awake rat.
The present study was aimed to investigate the effects of a chronic treatment with the dopamine uptake blocker nomifensine on the in vivo extracellular concentrations of dopamine, acetylcholine, glutamate and GABA in the prefrontal cortex, striatum and nucleus accumbens. Male Wistar rats received intraperitoneal (i.p.) daily injections of nomifensine (10 mg/kg) or saline for 22 days. Microdialysis experiments were performed on days 1, 8, 15 and 22 of treatment to evaluate the effects of the injection of nomifensine or saline. Motor activity of the animals was monitored during microdialysis experiments. Injections of nomifensine increased extracellular concentration of dopamine in striatum and nucleus accumbens, but not in prefrontal cortex. Acetylcholine concentrations in striatum but not in nucleus accumbens were increased by nomifensine on days 15 and 22 of treatment. In prefrontal cortex, nomifensine increased acetylcholine levels without differences among days. No changes were found on glutamate and GABA concentrations in the three areas studied. Injections of nomifensine also increased spontaneous motor activity and stereotyped behaviour without differences among days. These results show that systemic chronic treatment with a dopamine uptake blocker produces differential effects on extracellular concentrations of dopamine and acetylcholine, but not glutamate and GABA, in different areas of the brain.
Hernández
L F
LF
Department of Physiology, Faculty of Medicine, Universidad Complutense, Ciudad Universitaria s/n, 28040 Madrid, Spain.
Segovia
G
G
Mora
F
F
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009627:Nomifensine / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D009627:Nomifensine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D004298:Dopamine