Methysergide releases locomotion without support in lateral hypothalamic akinesia

Rats made profoundly akinetic by large bilateral electrolytic partial transections of the lateral hypothalamus were released from their akinesia by methysergide maleate (45 mg/kg, IP). When tested as soon as 24 hr postoperatively, lateral hypothalamic rats treated with methysergide displayed vigorous forward locomotion without postural support for as long as an hour and a half. By postoperative day 5, the locomotion elicited by methysergide was integrated with postural support to produce a more normal form of walking. Although atropine sulfate (50 mg/kg, IP) releases excessive walking in akinetic rats treated with 6-hydroxydopamine [53] it did not release locomotion lateral hypothalamic rats. Similarly, apomorphine, clonidine and phentolamine did not do so. Assuming that methysergide in the dose used exerts its effects primarily via the blockade of serotonin systems, we suggest that, in addition to an inhibitory cholinergic system, an independent inhibitory serotonergic system may also exaggerate the akinesia seen following treatments that diminish the action of brain catecholamine systems. Furthermore, the type of locomotion released by methysergide is a fractional form not previously isolated.