NMDA-mediated metabolic activation of the cerebellar cortex in behaving rats by the neuropeptide endothelin-1.

Generalized barrel-rolling convulsions and focal hypermetabolic responses in the cerebellar cortex of conscious rats to lateral ventricular injection of the neuropeptide, endothelin-1 (ET; 9 pmol), were diminished or eliminated by i.c.v. pretreatment with the glutamatergic NMDA receptor antagonist, MK-801 (44 nmol). Using the quantitative autoradiographic [14C]deoxyglucose technique, we assessed rates of glucose metabolism in individual structures anatomically connecting forebrain nuclei within a polysynaptic network linked to the cerebellar cortex. Cerebellar cortical afferent sources from specific subnuclei of the inferior olivary complex, cuneate nucleus, and medial vestibular nucleus, all of which were hypermetabolic following injection of ET alone, were also inhibited by MK-801. The findings indicate that a convulsive i.c.v. dose of ET elicits an NMDA-related stimulatory effect, whose origin is probably at the periventricular caudate nucleus, that activates rates of glucose metabolism in several afferent sources and subregions of the cerebellar cortex involved in the regulation of equilibrium, posture, and the visuovestibular system.