Effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine) on schedule-controlled behavior and their reversal by 5-HT antagonists in the pigeon

Abstract

The effects of MK-212 (6-chloro-2[l-piperazinyl]pyrazine), a centrally-active 5-hydroxytryptamine (5-HT; serotonin) agonist, were studied alone and in combination with the 5-HT antagonists, methysergide (0.01–0.1 mg/kg), metergoline (0.01–1.0 mg/kg) and ketanserin (0.01–3.0 mg/kg). Pigeons were maintained under a procedure where key pecks were reinforced under a multiple fixed-interval (FI) fixed-ratio (FR) schedule of food presentation. In the fixed-interval component, the first response after 3 min had elapsed, produced food, while in the fixed-ratio component, the thirtieth response was reinforced. The drug MK-212 (0.1–3.0 mg/kg) produced dose-related decreases in response rates under both components of the schedule. In smaller doses of MK-212 (0.3 and 1.0 mg/kg), the decrease in the response rate was greater in the fixed-interval component than in the fixed-ratio component. Small doses of methysergide (0.03 mg/kg) and metergoline (0.1 mg/kg), which had little effect when given alone, partially blocked the effects of MK-212 (1.7 and 3.0 mg/kg) in decreasing rate. Larger doses of these compounds, which sometimes increased the response rate when given alone, resulted in a more complete restoration of response rates when administered with MK-212. Ketanserin, a selective 5-HT 2 antagonist, reversed the effects of MK-212 in some cases, but the patterning of responses remained disturbed. These results demonstrate that MK-212 was able to disrupt a complex behavioral task in the pigeon at doses which caused no other noticeable signs, and that these effects were reversed in a systematic way by serotonin antagonists, known to exert a similar antagonism of the effects of MK-212 on other behavioral responses.