Clearance and diffusion of locally applied dopamine in normal and 6-hydroxydopamine-lesioned rat striatum.
Studies of dopamine (DA) clearance and diffusion were carried out after unilateral destruction of striatal DA afferents using intraparenchymal injection of 6-hydroxydopamine (6-OHDA). Rats were screened for the extent of DA depletion by testing for contralateral rotations induced by 0.05 mg/kg of apomorphine. Exogenous DA clearance and diffusion were determined using rapid (5 Hz) in vivo chronoamperometry with Nafion-coated carbon-fiber electrodes. Local applications of DA by pressure ejection from micropipettes into the lesioned vs. nonlesioned striata, with dose adjusted to elicit roughly equivalent amplitudes of electroactive signals, manifested a much prolonged clearance time on the lesioned side. A second protocol involved administration of equal volumes (amounts) of DA into lesioned vs. nonlesioned striata. In such cases, a volume of DA which manifested no detectable signal on the intact side produced a pronounced electrochemical signal on the lesioned side. When nomifensine, a high-affinity DA uptake inhibitor, was locally applied into the intact striatum, a subsequent ejection of DA produced a much larger signal than when the same volume was given before nomifensine. Very little or no effects of nomifensine were seen in 6-OHDA-lesioned striata. Taken together, these data indicate a much prolonged clearance time of DA in 6-OHDA-denervated striata. Moreover, the data also suggest that the primary mechanism underlying this effect is the loss of high affinity neuronal uptake. Thus, such changes in DA clearance may help account for some of the well documented compensatory phenomena which occur after DA-depleting lesions in animals and in man.
van Horne
C
C
Department of Pharmacology, University of Colorado Health Sciences Center, Denver.
Hoffer
B J
BJ
Strömberg
I
I
Gerhardt
G A
GA
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004058:Diffusion; D004298:Dopamine / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D009627:Nomifensine / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley
D009627:Nomifensine; D016627:Oxidopamine; D004298:Dopamine