The effect of chronic L-dopa administration on supersensitive pre- and postsynaptic dopaminergic receptors in rat brain.
Chronic administration of haloperidol induced supersensitivity of the pre- and postsynaptic dopaminergic receptors in rat brain. The response of the presynaptic receptors was determined by an enhanced inhibitory effect of apomorphine on dopamine synthesis after gamma-butyrolactone injection. This change in the receptor function was detected both in the nigrostriatal and mesolimbic pathways. Haloperidol also increased the 3H-spiperone binding sites in striatal membranes, indicating supersensitivity of the postsynaptic receptors. Subsequent prolonged treatment with high doses of L-DOPA/carbidopa resulted in a decrease in 3H-spiperone binding sites, but had no effect on the supersensitive presynaptic receptors. It is suggested that tardive dyskinesia may be a state of both pre- and postsynaptic dopamine receptor supersensitivity and that chronic L-DOPA treatment may have a differential effect on these sites.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D006834:Hydrazines; D011954:Receptors, Dopamine; D007980:Levodopa; D013134:Spiperone; C004297:3-hydroxybenzylhydrazine; D006220:Haloperidol