dizocilpine-maleate and Choline-Deficiency

In the present study, we investigated whether the essential nutrient choline may protect against schizophrenic-like cognitive deficits in a rat model. Theories regarding the etiology of schizophrenia suggest that early life events render an individual more vulnerable to adult challenges, and the combination may precipitate disease onset. To model this, the adult male offspring of dams who either experienced stress during late gestation or did not were given a 5 mg/kg dose of the NMDA antagonist,MK-801. The presence of both the prenatal challenge of stress and the adult challenge of MK-801 was expected to impair memory in these offspring. Memory was not expected to be impaired in rats that did not experience prenatal stress, but did receive MK-801 as adults. To study whether choline levels altered outcomes in these groups, rats were fed a choline-supplemented, -deficient, or standard diet during the period between the two challenges: beginning at weaning and continuing for 25 days. All rats consumed regular rat chow thereafter. The efficacy of the model was confirmed in the standard fed rats in that only those that were prenatally stressed and received MK-801 as adults displayed impaired memory on a novelty preference test of object recognition. Contrary to this finding and consistent with our hypothesis, choline-supplemented rats that were also both prenatally stressed and given MK-801 as adults showed intact memory. Choline deficiency impaired memory in rats that were just prenatally stressed, just given MK-801 as adults, and subjected to both. Thus, a choline deficient diet may render rats vulnerable to either challenge. Taken together, we offer evidence that developmental choline levels modulate the effects of prenatal stress and/or MK-801 and thereby alter the cognitive outcome in a rat model of schizophrenia.

Topics: Animals; Choline; Choline Deficiency; Cognition Disorders; Disease Models, Animal; Dizocilpine Maleate; Eating; Excitatory Amino Acid Antagonists; Exploratory Behavior; Female; Male; Motor Activity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Long-Evans; Schizophrenia; Schizophrenic Psychology; Stress, Physiological

The availability of choline during the prenatal period influences neural and cognitive development. Here we report that choline supplementation during a six-day gestational period protects against neurodegeneration in the posterior cingulate and retrosplenial cortices of adult female rats produced by systemic administration of the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801). These data show that availability of choline during a brief prenatal period diminishes vulnerability to neurotoxicity in adult offspring.

Topics: Animals; Animals, Newborn; Cerebral Cortex; Choline; Choline Deficiency; Diet; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Female; Gyrus Cinguli; Neurons; Nootropic Agents; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley