DOPAMINE AGONIST-INDUCED INHIBITION OF NEUROTRANSMITTER RELEASE FROM THE AWAKE SQUIRREL-MONKEY PUTAMEN AS MEASURED BY MICRODIALYSIS

Male squirrel monkeys (Saimiri sciureus) were surgically prepared with cranial guide cannulae for acute microdialysis sampling of the putame n nucleus, a dopamine (DA)-rich brain region. On the day of an experim ent, an animal was placed in a Plexiglas restraining chair and a micro dialysis probe was inserted through the guide into the putamen. Perfus ates of artificial cerebrospinal fluid were collected every 20 min ove r several hours and analyzed via HPLC with electrochemical detection, DA D-2/D-3 agonist drugs were administered either orally (p.o.) or sub cutaneously (s.c.), and changes in levels of DA in the dialysates were measured. All of the drugs tested, i.e., quinpirole (0.5 mg/kg p.o.), talipexole (0.75 mg/kg p.o. or s.c.), and PD 135222 (7 mg/kg p.o.), d ecreased spontaneous DA overflow by similar to 40-50% during the first 2 h following dosing, In animals that routinely underwent the microdi alysis procedure up to 23 times over a 2-year period, there was neithe r an appreciable change in basal DA overflow nor a significant change in the magnitude of drug response. These data suggest that DA D-2/D-3 agonists attenuate DA neuronal overflow in the primate brain, similar to effects seen in rodents. Furthermore, these results also demonstrat e the utility of repeated intracerebral microdialysis as a tool to mon itor dynamic changes in neurochemical activity in monkeys over a prolo nged period of time.