Chronic lithium administration alters behavioral recovery from nigrostriatal injury: effects on neostriatal [3H]spiroperidol binding sites.
Unilateral damage to the mesotelencephalic dopaminergic projection of the rat produces impairments in sensorimotor functions, including an inability to localize contralateral somatosensory stimuli. Many rats with 6 hydroxydopamine injections along this pathway show a gradual improvement in somatosensory localization during the first post-operative month. One mechanism that may contribute to this behavioral recovery is the proliferation of dopamine receptor sites in the affected neostriatum. The role of these binding site changes in the recovery was tested by chronic administration of lithium to rats. Rats given lithium in their drinking water for 4 weeks after the 6-hydroxydopamine injection showed a greatly attenuated recovery of sensorimotor functions, compared to brain-damaged rats drinking unadulterated water. When rats that were given lithium for the first four postoperative weeks were subsequently given unadulterated water to drink, they recovered normally. Lithium treatment did not prevent the augmentation of [3H]spiroperidol binding in the neostriatum ipsilateral to the lesion, relative to the contralateral control neostriatum, at 4 or 8 weeks post-operatively. Thus, lithium treatment dissociates behavioral recovery after nigrostriatal injury from the lesion-induced relative proliferation of neostriatal [3H]spiroperidol binding sites. However, the lithium treatment decreased the absolute amount of specific [3H]spiroperidol binding to both the ipsilateral and contralateral neostriata. The significance of these findings for the neural mechanism underlying this recovery sequence is discussed.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D016651:Lithium Carbonate; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects*; D014110:Touch / Q000187:drug effects
D002090:Butyrophenones; D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D016651:Lithium Carbonate; D013134:Spiperone; D016627:Oxidopamine; D008094:Lithium; D004298:Dopamine