Use of calcium antagonism for the characterization of drug-evoked dopamine release from the brain of conscious rats determined by microdialysis.
Dopamine was determined by microdialysis of the striatum of conscious rats. We investigated whether the release of dopamine, induced by nine different pharmacological treatments, was sensitive to calcium antagonism. Calcium antagonism was determined by Mg2+ or Cd2+ infusion. The following conditions were investigated: haloperidol, haloperidol plus GBR 12909, nomifensine, (+)-amphetamine (all administered intraperitoneally), KCl, 1-methyl-4-phenyl-pyridinium ion (MPP+), glutamate, ouabain, and 120 mmol/L magnesium (all applied by infusion through the dialysis membrane). The results on calcium antagonism were combined with data on tetrodotoxin (TTX) sensitivity. With the combined data, three different types of dopamine release were characterized. First, action potential-dependent dopamine release was observed in animals treated with saline, haloperidol, haloperidol plus GBR 12909, nomifensine, and ouabain. Second, action potential-independent release was established in the case of (+)-amphetamine, glutamate, MPP+, and 120 mmol/L Mg2+. Finally, K+-induced dopamine release was classified as TTX independent and calcium dependent. It is concluded that brain dialysis is a powerful method for differentiating between different types of neurotransmitter release.
Westerink
B H
BH
Department of Medicinal Chemistry, University of Groningen, The Netherlands.
Hofsteede
R M
RM
Tuntler
J
J
de Vries
J B
JB
D015655:1-Methyl-4-phenylpyridinium; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D010879:Piperazines; D011726:Pyridinium Compounds; D015102:3,4-Dihydroxyphenylacetic Acid; D009627:Nomifensine; D018698:Glutamic Acid; D013779:Tetrodotoxin; D010042:Ouabain; C043425:vanoxerine; D000661:Amphetamine; D008274:Magnesium; D006220:Haloperidol; D015655:1-Methyl-4-phenylpyridinium; D011188:Potassium; D002118:Calcium; D004298:Dopamine