Depolarization inactivation of dopamine neurons: terminal release characteristics.
The functional consequences of chronic treatment with haloperidol (0.5 mg/kg s.c. for 21-23 days) on striatal extracellular levels of dopamine and excitatory amino acids, aspartate and glutamate, were examined using microdialysis techniques. Our studies indicate that, in both awake and anesthetized animals, chronic haloperidol treatment does not appear to change basal outflow of dopamine and its response to an exogenous antagonist (i.e., a challenge dose of haloperidol). Furthermore, in chronic haloperidol and vehicle-treated animals, extracellular dopamine levels were decreased below our limit of detection following perfusion of tetrodotoxin through the probe, or into the medial forebrain bundle, suggesting that in both groups of animals extracellular dopamine levels are neuronally derived and seemed to depend equally on impulse flow. However, some differences were observed between the vehicle and haloperidol-treated animals: the excitatory action of 30 mM K+ on extracellular dopamine levels was decreased, and extracellular levels of glutamate were significantly increased, in animals treated chronically with haloperidol. The alterations in extracellular glutamate levels suggests that events at the terminal may be involved in maintaining the "normal" extracellular dopamine levels. Furthermore, the decrease in response to stimulation by K+ suggests that chronic haloperidol treatment may decrease the responsivity of the striatal dopamine system to stimuli.
Moghaddam
B
B
Department of Psychiatry, Yale University School of Medicine, West Haven, Connecticut.
Bunney
B S
BS
D000768:Anesthesia, General; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003243:Consciousness; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine