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 putamen nucleus, a dopamine (DA)-rich brain region. On the day of an experiment an animal was placed in a Plexiglas restraining chair and a microdialysis probe was inserted through the guide into the putamen. Perfusates of artificial cerebrospinal fluid were collected every 20 min over several hours and analyzed via HPLC with electrochemical detection. DA D2/ D3 agonist drugs were administered either orally (p.o.) or subcutaneously (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.), decreased spontaneous DA overflow by approximately 40-50% during the first 2 h following dosing. In animals that routinely underwent the microdialysis procedure up to 23 times over a 2-year period, there was neither an appreciable change in basal DA overflow nor a significant change in the magnitude of drug response. These data suggest that DA D2/D3 agonists attenuate DA neuronal overflow in the primate brain, similar to effects seen in rodents. Furthermore, these results also demonstrate the utility of repeated intracerebral microdialysis as a tool to monitor dynamic changes in neurochemical activity in monkeys over a prolonged period of time.
Davis
M D
MD
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, Michigan, USA.
Heffner
T G
TG
Cooke
L W
LW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D003243:Consciousness; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D017551:Microdialysis; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011699:Putamen / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D012453:Saimiri; D013779:Tetrodotoxin / Q000494:pharmacology
D001381:Azepines; D018491:Dopamine Agonists; D018377:Neurotransmitter Agents; C103913:PD 135222; D011725:Pyridines; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; D019257:Quinpirole; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; C024763:talipexole; D004298:Dopamine