title: Long-term decreases in striatal dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid after a single injection of amphetamine in iprindole-treated rats: time course and time-dependent interactions with amfonelic acid.
abstract: The administration of a single dose of (+)-amphetamine sulfate (9.2 mg/kg) to rats treated with iprindole hydrochloride (10 mg/kg) produced marked decreases in the striatal concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) one week after drug administration. Significant changes were not observed in striatal 5-hydroxyindoleacetic acid (5-HIAA) nor in norepinephrine, DA, DOPAC, HVA, and 5-HIAA concentrations in frontal cortex and a limbic forebrain sample containing primarily nucleus accumbens and olfactory tubercles. In time-course experiments, decreases in striatal DA were apparent by 12 h after amphetamine plus iprindole administration and persisted for at least 4 weeks. Decreases in striatal DOPAC and HVA followed a similar time course, except decreases in these parameters were observed at 6 h as well. The administration of amfonelic acid, a potent DA uptake inhibitor, up to 8 h but not at 12 h after amphetamine administration prevented the decreases in striatal DA, DOPAC and HVA at on week after the administration of the drug to iprindole-treated rats. These data indicate that the actions of amphetamine which are necessary and sufficient for the production of long-term decreases in striatal DA, DOPAC and HVA are dependent upon the integrity of the neuronal uptake mechanism for DA and occur within 12 h after the administration of amphetamine to iprindole-treated rats. Although amfonelic acid prevented the long-term effects of amphetamine on striatal DA neurons, it did not alter the decrease in DOPAC produced by amphetamine at 6 h after the administration of amphetamine plus iprindole. This finding suggests that the ability of amfonelic acid to prevent the long-term effects of amphetamine on striatal DA neurons in iprindole-treated rats is not due to a blockade of the entry of amphetamine into the neuron and, thus, suggests that the access of amphetamine to the inside of the neuron is not sufficient for the production of its long-term, possibly neurotoxic, effects n striatal DA neurons.
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D007488:Iprindole / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009268:Nalidixic Acid / Q000031:analogs & derivatives; D009287:Naphthyridines / Q000494:pharmacology*; D009928:Organ Specificity; D010648:Phenylacetates / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007211:Indoles; D009287:Naphthyridines; D010648:Phenylacetates; D015102:3,4-Dihydroxyphenylacetic Acid; D009268:Nalidixic Acid; D007488:Iprindole; C006486:amfonelic acid; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid