The striatal transporter for dopamine in the rat may be kinetically up-regulated following 3 weeks of withdrawal from cocaine self-administration.
Rotating disk electrode voltammetry was used to measure the inwardly directed Vmax and Km of dopamine with its transporter in striatal suspensions prepared from nonhandled control rats, rats that had been trained to self-administer cocaine for 20 days (at 26 mg/day per rat) via a jugular catheter and subsequently withdrawn for 3 weeks, and rats that had received saline (155 mM NaCl) via a jugular catheter on the same schedule as the rats that had received cocaine. Because a limited number of animals was available from the self-administration procedure, the velocity of dopamine transport as a function of [dopamine] was measured by incremental addition of dopamine to a given striatal preparation. In nonhandled controls the values of Vmax, Km, and turnover, observed in this experimental paradigm, were increased relative to results obtained in studies of the velocity-[dopamine] relationship where dopamine was added to suspensions, one concentration per suspension. The kinetics of the association of dopamine with the transporter were unchanged. The Vmax to Km ratios obtained in the two experiments were statistically indistinguishable, suggesting that the two types of experiments probe the same transporter. Also, the increased velocity observed in the experiment involving sequential additions to the same preparation is evidence of trans acceleration, suggesting that the movement of dopamine across the membrane is carrier mediated as opposed to being mediated via channels or pores and that the rate-limiting step in inwardly directed transport is the reorientation of the unloaded transporter from the inwardly to the outwardly facing forms.(ABSTRACT TRUNCATED AT 250 WORDS)
Meiergerd
S M
SM
Department of Chemistry, Washington State University, Pullman 99164-4630.
Hooks
S M
SM
Schenk
J O
JO
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D003042:Cocaine; D004298:Dopamine