In order to clarify the mechanisms by which
nicotinic acid deficiency impairs brain function, the effects of the
nicotinic acid antimetabolite,
3-acetylpyridine, have been investigated on behavior, cerebral oxidative metabolism, and
acetylcholine synthesis. In young rats (21-23 days old),
3-acetylpyridine caused dose- and time-related deficits in behavior, as measured by a neurological scale and by "tight-rope" performance, loss of
body weight, and decreased survival. An intermediate dosage decreased cerebral
glucose utilization in the inferior olivary nuclei, but increased it in the fastigial, interpositus, red, dentate, vestibular, posterior mamillary, and habenular nuclei. Selective alteration of metabolism was also observed in brain slices from 3-acetylpyridine-treated rats. Although forebrain slices were unaffected, in brainstem slices the synthesis of
acetylcholine decreased by 34% with depolarizing (31 mM) concentrations of K+ (P less than 0.05). This dose of
3-acetylpyridine did not deplete the total pool of
NAD in any of the 7 brain regions examined. Thus, the
nicotinic acid deficiency which results from
3-acetylpyridine treatment appears to be yet another
metabolic encephalopathy in which
cholinergic systems are impaired.