Stress-induced neurological impairments in an animal model of parkinsonism.
Adult rats were given the neurotoxin 6-hydroxydopamine (6-HDA) by means of cerebrospinal fluid to produce large dopamine-depleting brain lesions. Although the animals behaved normally in their home cages, they became akinetic after such treatments as glucoprivation, tail shock, and exposure to severe cold. The neurological impairments were related both to the extent of dopamine depletion and to the intensity of the stress. Drugs known to enhance dopaminergic function were found to reverse the stress-induced neurological deficits, while dopaminergic antagonists potentiated the debilitating effects of stress. After focal lesions were produced by injecting 6-hydroxydopamine directly into specific brain regions, stress-induced akinesia was found to correlate best with dopamine depletion in the corpus striatum, especially the lateral portion of that structure. These and other findings suggest that the acute emergence of parkinsonian symptoms during stress may reflect extensive damage to the dopaminergic nigrostriatal pathway that had been concealed in a preclinical phase, owing to compensatory neurochemical changes in the dopaminergic neurons that yet remain intact.
D000818:Animals; D016642:Bupropion; D003342:Corpus Striatum / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010293:Pargyline / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D011427:Propiophenones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013312:Stress, Physiological / Q000150:complications*
D006892:Hydroxydopamines; D011427:Propiophenones; D011954:Receptors, Dopamine; D016642:Bupropion; D016627:Oxidopamine; D003847:Deoxyglucose; D010293:Pargyline; D003891:Desipramine; D004298:Dopamine; D009638:Norepinephrine