In vivo electrochemical measurements of exogenous dopamine clearance in normal and neonatal 6-hydroxydopamine-treated rat striatum.
The regulation of extracellular dopamine (DA) levels was studied in rat striatum after neonatal dopamine lesions and enhanced serotonin (5-HT) fiber ingrowth, induced with 6-hydroxydopamine (6-OHDA). We used rapid in vivo chronoamperometry combined with local DA applications. DA was pressure ejected in doses of 5 to 100 pmol at a distance of approximately 300 microns from the recording electrode, using single- or multibarrel glass micropipettes. Almost twice as much DA had to be applied in control rat dorsal and ventral striatum to obtain signals comparable to those recorded in the neonatal 6-OHDA-treated animals. In addition, in the dorsal striatum, the later portions of the DA clearance signals were significantly prolonged in the 6-OHDA group. Some clearance decay times in ventral striatum were also significantly prolonged in the neonatal 6-OHDA-treated rats. Concomitant application of the DA uptake inhibitor, nomifensine, in conjunction with the DA ejections, produced signal characteristics in the control striatum that were similar to those seen in the neonatal 6-OHDA-treated striatum. Taken together, these data support the hypothesis that a major component of the clearance of extracellular DA is dependent on intact terminals with high-affinity DA uptake, and that loss of DA afferents from neonatal 6-OHDA treatment results in a slowed clearance time of extracellular DA which is not apparently compensated by the enhanced 5-HT fiber ingrowth.
Luthman
J
J
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Friedemann
M N
MN
Hoffer
B J
BJ
Gerhardt
G A
GA
D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000493:pharmacokinetics*; D004563:Electrochemistry; D008297:Male; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors
D009627:Nomifensine; D016627:Oxidopamine; D004298:Dopamine