Lack of effect of dopamine receptor blockade on SKF83959-altered operant behavior in male rats.

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Dopamine (DA) is important for the performance of operant behavior as revealed by psychopharmacological studies that manipulate the activity of DA subtype receptors. However, the effects of SKF83959, an atypical DA D1 receptor agonist, on operant behavior and the underlying pharmacological mechanisms remain unclear. The present study sought to determine whether blockade of DA D1- and D2-subtyped receptors would reverse the operant behavior altered by SKF83959. Male rats were trained to respond on either a fixed-interval 30 s (FI30) schedule or a differential reinforcement of low-rate response 10 s (DRL10) schedule, two timing-relevant tasks but with distinct reinforcement contingencies. Pharmacological evaluation was conducted with injection of a selective D1 (or D2) receptor antagonist alone or in combined with SKF83959 (1.0 mg/kg) following a stable baseline of behavioral performance. The results showed that SKF83959 treatment alone significantly disrupted the performance of FI30 and DRL10 behaviors mainly by showing the decreases of the response-related measures, and the distinct profiles of the behavior altered by the drug were manifested by the qualitative analysis of inter-response time data on both tasks. The effects of SKF83959 were not significantly affected/reversed by the pretreatment of either SCH23390 or eticlopride injected at the doses of 0.02 and 0.06 mg/kg; however, a subtle reversal effect was observed in the treatment of low-dose eticlopride. Despite that these results confirm the FI30 and DRL10 behaviors changed by SKF83959, the absence of pharmacological reversal effect by DA receptor antagonist suggests that either D1- or D2-subtyped receptors may not play a critical role in the alteration of timing-relevant operant behavior produced by SKF83959.