Neurochemical effects of prolonged treatment with remoxipride as assessed by intracerebral microdialysis in freely moving rats.
1. At three microdialysis sessions, dialysates were collected from the striatum of the same rats. 2. Microdialysis session 1. A single s.c. injection of remoxipride (40 mumol/kg), resulted in increased dialysate concentrations of dopamine, DOPAC and HVA. 3. Microdialysis session 2. Continuous administration of remoxipride (8.6 mumol/rat/day) for 14 days, using mini-osmotic pumps, produced maintained elevated levels of dopamine, DOPAC and HVA. 4. Microdialysis session 3. A challenge dose of remoxipride (40 mumol/kg s.c.), given to the rats after a 48-hour wash-out period following the continuous remoxipride treatment, increased the dialysate concentrations of dopamine, DOPAC and HVA to similar extent as at dialysis session 1. 5. It is concluded that after long-term treatment of remoxipride, an adaptation of the basal state of the DA system appears to take place, implying a lowering of basal DA release and DA metabolism. However, the capacity to respond with increased DA release and DA metabolism to renewed remoxipride treatment is retained, indicating little, if any, tolerance.
Department of Neuropharmacology, Astra Arcus AB, Södertälje, Sweden.
J
J
Georgieva
B
B
Mohringe
O
O
Magnusson
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D004361:Drug Tolerance; D006719:Homovanillic Acid / Q000378:metabolism; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017330:Remoxipride / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D017330:Remoxipride; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid