6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1- and D2-dopamine agonists into nucleus accumbens and striatum without changing dopamine antagonist binding.
Behavioral responses to D1 and D2-dopamine agonists are enhanced when these agonists are administered systemically to 6-hydroxydopamine (6-OHDA)-lesioned rats. In the present investigation, microinjection of SKF-38393, a D1-dopamine agonist, into the nucleus accumbens of adult rats lesioned as neonates with 6-OHDA produced a dose-related increase in locomotor activity that was enhanced markedly compared to control. LY-171555, a D2-agonist, elicited less locomotor activity than did SKF-38393 after microinjection into this site. Administration of SKF-38393 or LY-171555 into the nucleus accumbens did not increase locomotion in unlesioned rats at the doses administered to lesioned animals. In adult-6-OHDA-lesioned rats, microinjection of SKF-38393 into the nucleus accumbens also increased locomotion more than did LY-171555. As described previously, systemic administration of SKF-38393 produced little locomotion in adult-6-OHDA-lesioned rats, whereas LY-171555 produced a markedly enhanced response. Administration of SKF-38393 or LY-171555 into the caudate nucleus of neonatally and adult-6-OHDA-lesioned rats produced negligible locomotor activity, but did induce stereotypic behaviors similar to those observed after systemic treatment with these drugs. Stereotypic behaviors occurred to a greater degree in the 6-OHDA-lesioned rats than in unlesioned controls. A regional specificity for certain behaviors induced by dopamine agonist administration was observed. In spite of the enhanced behavioral responses of D1 and D2-dopamine agonists after microinjection into the brain of 6-OHDA-lesioned rats, binding of [3H]spiperone (D2-receptor antagonist ligand) and [3H]SCH 23390 (D1-receptor antagonist ligand) to tissue from striatum and nucleus accumbens was not altered significantly. In contrast to this lack of change in binding characteristics in 6-OHDA-lesioned rats, blockade of dopaminergic transmission with haloperidol treatment caused an elevation of [3H]spiperone binding sites in striatum without affecting affinity for the site. However, chronic haloperidol treatment did not alter significantly [3H]SCH 23390 binding to striatal membranes. These latter findings suggest that chronic dopamine receptor blockade need not produce the same adaptive mechanisms as destruction of dopamine-containing neurons. Thus, a change in receptor characteristics as measured by dopamine antagonist binding does not account for the behavioral supersensitivity observed after D1- and D2-dopamine agonist administration to neonatally or adult-6-OHDA-treated rats.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007650:Ketanserin / Q000494:pharmacology; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects*; D016627:Oxidopamine; D011247:Pregnancy; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; D004873:Ergolines; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D019257:Quinpirole; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D007650:Ketanserin; D004298:Dopamine