Reversible decrease in dopaminergic 3H-agonist binding after 6-hydroxydopamine and irreversible decrease after kainic acid.
Six days after the unilateral intrastriatal injection of 30 ug 6-hydroxydopamine (6-OHDA) the number of stereospecific 3H-dopamine and 3H-apomorphine binding sites (Bmax) was reduced by 50-60% in the caudate nucleus ipsilateral to the lesion. The dopamine content of the lesioned caudate nucleus was also reduced to 2% of the contralateral side or of sham-operated controls. The preincubation of depleted homogenates with added dopamine reversed the effects of 6-OHDA on the Bmax of 3H-agonists. A similar pattern of depletion, decrease in binding and in vitro reversal by dopamine was observed after a single injection of reserpine (4.0 mg/kg, im.). The intrastriatal injection of kainic acid also lowered the Bmax of 3H-agonists by 65% without altering dopamine content. Preincubation of homogenates of kainic acid-lesioned caudate nuclei with 355 nM (endogenous) dopamine did not reverse the decrease in binding. We conclude that treatments which deplete endogenous dopamine, including the lesion of nigrostriatal terminals, induce a reversible change in the parameters of 3H-agonist binding whereas the destruction of intrinsic caudate neurons with kainic acid results in an irreversible loss of receptors.
D000818:Animals; D001058:Apomorphine / Q000378:metabolism*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D006892:Hydroxydopamines / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D016627:Oxidopamine; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D006892:Hydroxydopamines; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D014316:Tritium; D016627:Oxidopamine; D001058:Apomorphine; D007608:Kainic Acid; D004298:Dopamine