The effects of cortical ablation on d-amphetamine-induced changes in striatal dopamine turnover and ascorbic acid catabolism in the rat.
Dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA) and dehydroascorbic acid (DHAA) levels were determined by HPLC in the striatal synaptosomal fraction and in the whole striatum of rats, whose fronto-parietal cortex had been bilaterally ablated, after a single injection of d-amphetamine (2.0 mg/kg i.p.). d-Amphetamine significantly increased the DHAA/AA ratio in unoperated and sham-operated rats, but failed to increase it in ablated rats, as compared to pertinent saline-treated groups. In the synaptosomal fraction, d-amphetamine significantly decreased the DHAA/AA ratio in unoperated, sham-operated and ablated rats. d-Amphetamine significantly decreased the DOPAC/DA ratio in the whole striatum and significantly increased it in the striatal synaptosomal fraction in all experimental groups. Cortical ablation greatly increased d-amphetamine-induced motor hyperactivity. We conclude that the d-amphetamine-induced increase in AA striatal oxidation requires integrity of the cortico-striatal glutamatergic pathways. Further, AA oxidation occurs in the extracellular space. The cortico-striatal glutamatergic pathways exert an inhibitory modulation on d-amphetamine behavioral effects.
Desole
M S
MS
Institute of Pharmacology, University of Sassari, Italy.
Miele
M
M
Enrico
P
P
Fresu
L
L
Esposito
G
G
De Natale
G
G
Miele
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D001205:Ascorbic Acid; D003913:Dextroamphetamine; D004298:Dopamine; D003683:Dehydroascorbic Acid