Effects of clonidine and some alpha-adrenergic antagonists alone and in combination on schedule-controlled behavior...

Schedule-controlled responding was maintained under multiple fixed-interval, fixed-ratio schedules in pigeons and single fixed-ratio schedules in mice. In pigeons, clonidine, an alpha 2-receptor agonist, produced dose-related decreases in responding under both fixed-interval and fixed-ratio schedules; fixed-interval responding was decreased at a lower dose than fixed-ratio responding. Low to intermediate doses of yohimbine, and alpha 2-receptor antagonist, increased responding under the fixed-interval schedule without appreciably affecting responding under the fixed-ratio schedule; higher doses decreased responding under both schedules. In mice, both clonidine and yohimbine produced dose-related decreases in responding under fixed-ratio schedules. Decreases in response rates produced by clonidine were antagonized by low to intermediate doses of yohimbine. Decreases in response rates under fixed-ratio schedules produced by yohimbine were antagonized only slightly, if at all, by clonidine. Under the fixed-interval schedule, clonidine potentiated the response-rate increasing effects of intermediate doses of yohimbine and slightly antagonized the rate-decreasing effects. Although some effects of clonidine were antagonized by yohimbine, at no dose combination did performances completely resemble control performances. Prazosin, an alpha 1-receptor antagonist, was ineffective both when administered alone and as an antagonist of the effects of clonidine. The behavioral effects of clonidine appeared to be mediated by alpha 2 rather than alpha 1 receptors. Additionally, yohimbine appears to have significant behavioral effects other than alpha 2-antagonist actions.