The influence of priming on the behavioral expression of dopamine receptor supersensitivity in basal ganglia

The D-1 agonist SKF 38393 (2 mg/kg s.c.) failed to induce contralateral turning in drug-naive rats, lesioned unilaterally with 6-hydroxydopamine (6-OHDA) from 17 days, while elicited intense contralateral turning 90 days post lesion. Priming with a single administration of a dopaminergic (DA) agonist which elicited contralateral turning by itself, made SKF 38393 very active in producing contralateral turning in rats, lesioned with 6-OHDA from 17 days. The effectiveness of the D-1/D-2 agonist apomorphine as a primer of SKF 39393 induced turning was critically dependent on the interval between the administration of the two agonists. Effectiveness was minimal with an interval of 3 h, increased after 6–12 h, peaking at 72 h and was reduced after 10 days. Priming took place also when the primer and SKF 38393 were administered in different environment, indicating that priming in not dependent from behavioral conditioning. Finally, administration of the N-Methyl-D-Aspartate (NMDA) receptor antagonist (+) MK 801 in conjunction with apomorphine prevented its ability to act as a primer, indicating that the NMDA receptors exert a permissive role on priming