Behavioral responsitivity to dopamine receptor agonists after extensive striatal dopamine lesions during development.
Dopamine (DA) receptor responsitivity was investigated in adult rats that received intrastriatal (i.s.) injections of 6-OHDA (20 micrograms per striatum) on day of birth or postnatal Day 1 (Day 0/Day 1). Neonatally lesioned rats exhibited self-biting behavior and increases in stereotypic gnawing following treatment with the mixed D1/D2 receptor agonist apomorphine (0.32-3.2 mg/kg) or the D1-like receptor agonist SKF38393 (10 mg/kg). Increases in locomotor activity, rearing, and paw treading were also observed in the lesioned rats after SKF38393 (1-10 mg/kg) treatment. The incidences of the prototypical D1 receptor-mediated behaviors, grooming and abnormal perioral movements (i.e., oral dyskinesias) were not increased in the lesioned rats. However, the low dose (0.32 mg/kg) of apomorphien as well as all doses of the D2-like receptor agonist quinpirole (0.32-3.2 mg/kg) induced grooming in the lesioned rats, which was not observed in nonlesioned control rats. Autoradiographs of [3H]mazindol binding to high affinity DA uptake sites revealed an extensive loss of DA terminals in the striata of the neonatally lesioned rats. These data suggest that near-total (> or = 95%) DA depletions on Day 0/Day 1 result in long-term alterations in the functional sensitivity of DA receptors, as well as possible changes in the interactions between D1 and D2 receptors. Comparisons of these results with those seen following lesions of the early-developing DA system ("patch-selective" lesions) and lesions made at other time points will be discussed.
Neal-Beliveau
B S
BS
Department of Psychology, Indiana University Purdue University, Indianapolis 46202-3275, USA.
Joyce
J N
JN
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000293:injuries; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D003423:Critical Period, Psychological; D004298:Dopamine / Q000172:deficiency*; D018491:Dopamine Agonists / Q000145:classification / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D005260:Female; D006120:Grooming / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000187:drug effects / Q000502:physiology; D019370:Observation; D016627:Oxidopamine / Q000009:adverse effects; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D016728:Self-Injurious Behavior / Q000139:chemically induced; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine