Opposite influences of different adrenoceptors on baclofen-induced antinociception in mice.
M R Zarrindast
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In the present study, the effects of adrenoceptor agonists and antagonists on baclofen-induced antinociception was investigated. Intraperitoneal administration of different doses of baclofen (2.5, 5 and 10 mg/kg) induced antinociception in the tail-flick test. The response was dose-dependent. The alpha 2-adrenoceptor agonist, clonidine, increased, while the alpha 1-adrenoceptor agonist, phenylephrine, decreased the baclofen response. In reserpine-treated animals, alpha 2-adrenoceptor, clonidine, induced antinociception and increased that of baclofen. Yohambine and propranolol but not prazosin decreased the baclofen effect. Although phenoxybenzamine itself induced antinociception it did not alter the baclofen response significantly. Reserpine treatment decreased the response induced by single administration of baclofen or phenoxybenzamine and that induced by a combination of baclofen with either phenoxybenzamine or prazosin. It may be concluded that alpha 2-adrenoceptor stimulation increases, while alpha 1-adrenoceptor activation decreases the baclofen-induced antinociception, and aminergic mechanism(s) may have a positive influence on baclofen response.