The role of dopamine in the maintenance and breakdown of D1/D2 synergism.

The neurochemical factors involved in the maintenance and breakdown of dopamine D1/D2 receptor synergism were investigated by giving rats various pharmacological treatments that diminish the ability of dopamine to interact with its D1 and/or D2 receptors. Following these treatments, rats were observed for the expression of stereotyped motor behavior in response to independent stimulation of D1 or D2 receptors. Independent D2-mediated responses were observed: (a) 2 h after the last of three daily reserpine (1 mg/kg) injections, (b) 48 h after bilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathways, (c) 24 h after a concentrated 48-h regimen (one injection/6 h) of eticlopride (0.5 mg/kg) or eticlopride+SCH 23390 (0.5 mg each), and (d) 2 h after a concentrated 48-h regimen (one injection/6 h) of alpha-methyl-p-tyrosine (alpha MPT; 100 mg/kg), but not after control treatments or a concentrated regimen of SCH 23390 alone. By contrast, independent D1-mediated responses were observed only after three daily reserpine injections or 48 h after bilateral 6-OHDA lesions. Independent D1-mediated stereotypy was not observed under control conditions or following a concentrated 48-h regimen of (a) SCH 23390 or eticlopride (0.5 mg/kg each) alone or in combination, (b) a high dose of SCH 23390 (1.0 mg/kg), (c) alpha MPT (100 mg/kg), or (d) alpha MPT (100 mg/kg)+SCH 23390 (1.0 mg/kg). Reserpine, bilateral 6-OHDA, and alpha MPT treatments produced striatal dopamine depletions of 96%, 92%, and 71%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)