Priming of the Behavioral Expression of Dopamine-Receptor Supersensitivity in the Basal Ganglia: Pharmacological and Biochemical Studies
In drug-naive rats unilaterally lesioned with 6-hydroxydopamine (6-OHDA) from 17 days, stimulation of D-1 receptors by SKF 38393 (2 mg/kg s.c.) failed to induce contralateral turning. Administration, three days before, of a single dose of a dopaminergic agonist which elicited contralateral turning, made SKF 38393 very active in producing contralateral turning (priming). The effectiveness of the D-1/D-2 agonist apomorphine as a primer of SKF 38393-induced turning was critically dependent on the interval between the administration of the two agonists. Effectiveness was minimal after 3 h, increased after 6–12 h, peaked at 72 h and was reduced after 10 days. In drug-naive 6-OHDA lesioned rats, administration of the selective antagonists SCH 23390 (D-1) or raclopride (D-2) abolished apomorphine induced contralateral turning, while in primed rats both antagonists only modified the pattern of apomorphine turning but failed to abolish it. Analysis of D1 receptor binding in striata of drug-naive and primed rats, showed no change in the Bmax and Kd, while dopamine stimulated adenylate cyclase showed a decreased Km, for dopamine in the lesioned side after priming. Finally, administration of the N-Methyl-D-Aspartate (NMDA) receptor antagonist (+) MK 801 in conjunction with apomorphine, prevented the ability of apomorphine to act as a primer, indicating that the NMDA receptor exerts a permissive role on priming.
KeywordsAdenylate Cyclase Adenylate Cyclase Activity Medial Forebrain Bundle Lesion Side Permissive Role
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