1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine and 3-methoxytyramine

Intrastriatal kainic acid injection destroys the neurons originating from the striatum, including those on which terminals of the nigro- and meso-striatal dopaminergic neurons project. We have studied at various times the consequences of this lesion on dopamine metabolism and on the neuronal and vesicular transporters. Two and 15 days after kainic acid injection, whereas dopamine turnover was increased and the dopamine content unchanged, there was no modification in the binding of [3H]GBR 12783, a marker of the neuronal uptake complex, but the binding of [3H]dihydrotetrabenazine, a marker of the vesicular transporter, was significantly decreased. At later times (30 and 60 days) when the dopamine turnover was decreased as well as the dopamine content, the binding of [3H]dihydrotetrabenazine was more dramatically decreased (about 30% of controls) than that of [3H]GBR 12783. In addition autoradiography showed an increase in the density of [3H]dihydrotetrabenazine binding sites in the substantia nigra. Thus it appears that the long-term (60 days) repercussions of a kainic acid lesion affect simultaneously the dopamine turnover (which is decreased) and the vesicular transporter whereas the dopamine uptake complex is little affected.

Topics: 3,4-Dihydroxyphenylacetic Acid; Analysis of Variance; Animals; Autoradiography; Binding Sites; Biological Transport; Choline; Corpus Striatum; Dopamine; Dopamine Agents; Dopamine Plasma Membrane Transport Proteins; Homovanillic Acid; Kainic Acid; Male; Membrane Proteins; Microinjections; Nerve Tissue Proteins; Neurons; Piperazines; Rats; Rats, Sprague-Dawley; Synaptosomes; Tetrabenazine; Tritium

In mice, low doses (1-2-4 mg/kg s.c.) of dexamphetamine stimulated locomotor activity in a dose-dependent manner. Over the same range of doses the drug dose dependently inhibited the in vivo striatal binding of the dopamine uptake inhibitor, [3H]GBR 12783. At 3 mg/kg dexamphetamine, the stimulant effect and the inhibition of the striatal binding of [3H]GBR 12783 displayed a similar time course. Pretreatments that either increased (L-DOPA 200 mg/kg, benserazide 50 mg/kg i.p.) or decreased (reserpine 5 mg/kg s.c., alpha-methyl-p-tyrosine 200 mg/kg) striatal dopamine levels did not modify the inhibition by dexamphetamine of [3H]GBR 12783 binding in vivo. This suggests that the inhibition is due to a direct effect of dexamphetamine, not mediated by endogenous dopamine, and further that a unique site is responsible for the neuronal uptake of dexamphetamine and for the binding of pure dopamine uptake inhibitors.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Corpus Striatum; Dextroamphetamine; Dopamine; Dopamine Antagonists; Homovanillic Acid; Levodopa; Male; Mice; Motor Activity; Piperazines; Reserpine