Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of dexamphetamine.
Systemic administration of high doses of dexamphetamine induces a dopamine efflux that has its intracellular origin in both the vesicular, reserpine-sensitive dopamine pool and the cytosolic, alpha-methyl-para-tyrosine-sensitive, newly synthesized dopamine pool. It remains unknown whether locally administered dexamphetamine produces similar effects. Using a brain microdialysis technique that is combined with a microinjection needle, the contribution of the vesicular and cytosolic pools to the dopamine efflux induced by striatal injection of dexamphetamine was analyzed in rats. The transient striatal dopamine efflux induced by intrastriatal injection of dexamphetamine (1.0 microg/0.5 microl) was significantly reduced by systemic administration of reserpine (5mg/kg i.p., given 24 h earlier) or alpha-methyl-para-tyrosine (250 mg/kg i.p., given 2 h earlier). The effects of dexamphetamine on the striatal dopamine were nearly nullified by combined treatment with reserpine and alpha-methyl-para-tyrosine. The sum of the amounts of extracellular dopamine that was sensitive to either reserpine or alpha-methyl-para-tyrosine, was far greater than 100%, namely 146.1% of the basal dopamine level and 144.0% of the dexamphetamine-induced dopamine level. The present study indicates that both the vesicular dopamine pool and the cytosolic dopamine pool contribute to the transient increase of striatal dopamine efflux induced by intrastriatal injection of dexamphetamine. This study also suggests that striatally applied dexamphetamine can promote the redistribution of rat striatal dopamine from vesicles to the cytosol in vivo.
Watanabe
S
S
Department of Pharmacology, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Aono
Y
Y
Fusa
K
K
Takada
K
K
Saigusa
T
T
Koshikawa
N
N
Cools
A R
AR
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D003913:Dextroamphetamine / Q000008:administration & dosage* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000378:metabolism*; D019805:alpha-Methyltyrosine / Q000008:administration & dosage / Q000494:pharmacology
D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D019805:alpha-Methyltyrosine; D012110:Reserpine; D003913:Dextroamphetamine; D004298:Dopamine