In vivo dopamine release and uptake impairments in rats treated with 3-nitropropionic acid.
Recent evidence has suggested that mitochondrial dysfunction may lead to impaired neurotransmitter exocytosis in transgenic Huntington's disease (HD) model mice. To gain insight into the impact of mitochondrial impairment on striatal dopamine release in vivo, we used fast-scan cyclic voltammetry (FSCV) at carbon fiber microelectrodes to measure dopamine release and uptake kinetics in anesthetized Lewis rats continuously treated for 5 days with 3-nitropropionic acid (3NP). Our results indicate that, even though striatal dopamine content was unchanged, remotely stimulated dopamine release evoked per electrical stimulus pulse ([DA](p)) is decreased in 3NP-treated rats (33% of that observed in sham control rats) and that this decrease is uniform throughout all stereotaxic depths tested. Nevertheless, unlike data collected previously from transgenic HD model rodents, the maximum rate of dopamine uptake (V(max)) in 3NP-treated rats is diminished (30% of controls) while K(m) is unchanged. Treatment with 3NP also resulted in a corresponding decrease in locomotor activity, presumably due in part to the impaired dopamine release. These results indicate that dopamine release is degraded in this HD model, as is observed in transgenic HD model rodents; however, the results also imply that there are fundamental differences in dopamine uptake between 3NP-treated animals and transgenic animals.
Kraft
J C
JC
Department of Chemistry, The University of Kansas, Lawrence, KS 66045-7582, USA.
Osterhaus
G L
GL
Ortiz
A N
AN
Garris
P A
PA
Johnson
M A
MA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D006719:Homovanillic Acid / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008839:Microelectrodes; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009574:Nitro Compounds / Q000008:administration & dosage*; D011422:Propionates / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew
D002491:Central Nervous System Agents; D009574:Nitro Compounds; D011422:Propionates; D015102:3,4-Dihydroxyphenylacetic Acid; C015392:3-nitropropionic acid; D004298:Dopamine; D006719:Homovanillic Acid