Prevention of reserpine rigidity by alpha-2 adrenergic antagonists

Since alpha adrenergic antagonists are known to protect rats from the extrapyramidal effects of reserpine, the purpose of this study was to examine the relative contribution of alpha-2 receptors in modifying the reserpine-induced syndrome. Rats were pretreated with either clonidine, yohimbine, phentolamine, methysergide or SKF-7265. Thirty minutes later they were given reserpine (20 mg/kg) and evaluated using eleven categories of behavioral responses for three hours. Yohimbine, an alpha-2 antagonist, was the most effective agent in protecting against the reserpine effects. Phentolamine and SKF-7265, which block both alpha-1 and alpha-2 receptors, were also effective. Clonidine, an alpha-2 agonist, and methysergide a serotonin antagonist, were not. In all cases the alpha blocking drugs prevented the motor responses but did not alter the autonomic responses induced by reserpine. The results show not only the efficacy of alpha adrenergic antagonists in protecting against reserpine rigidity but more importantly that the blockade of alpha-2 receptors may be the functionally important action. These results are consistent with the view that some descending motor pathways are controlled by an adrenergic mechanism and suggest that alpha-2 receptors are an important component.