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Fetal Alcohol-Exposed Rats Exhibit Differential Response to Cholinergic Drugs on a Delay-Dependent Memory Task,☆☆

https://doi.org/10.1006/nlme.1999.3909Get rights and content

Abstract

Fetal alcohol exposure in human and rodents produces a number of cognitive deficits including impairments in learning and memory. Recent evidence in our laboratory has shown that fetal alcohol-exposed (FAE) rats respond differently to systemic administration of cholinergic drugs when tested for vigilance and locomotor activity. The present study examined the effects of muscarinic and nicotinic agonists and antagonists on memory performance in a delayed alternation task. Subjects were male offspring of Sprague-Dawley rats fed a 35% ethanol-derived caloric diet, pair-fed with sucrose, or chow-fed with lab chow during the last 2 weeks of gestation. Rats (3 months old) were food-deprived prior to training in the T-maze. Rats were first trained in the alternation task at no delay for five sessions. Rats were then trained at longer delays (20, 60, 180 s) until all groups showed similar performance for two consecutive sessions. Each animal was then tested following systemic injections of the cholinergic antagonists scopolamine and mecamylamine (60-s delay) and the cholinergic agonists pilocarpine and nicotine (180-s delay). Rats received saline injections on alternate days of testing. The results revealed that FAE rats exhibited no impairments in alternation performance at the no delay and 20-s delay, but showed impairments on both the 60- and 180-s delays during the initial sessions. However, with additional training, FAE rats showed performance similar to that of control groups at these delays. Following both pilocarpine and nicotine injections, control groups, but not the FAE group, showed significant memory enhancement in the alternation task. Following scopolamine injections, the FAE rats showed a significant impairment, while control groups showed a nonsignificant decrease in performance. All three groups showed impairments in the alternation task following administration of mecamylamine compared to saline treatment. These findings suggest that alterations in the cholinergic system in FAE rats may underlie some of the cognitive deficits observed with prenatal alcohol exposure.

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    This study was supported by National Institute on Alcohol Abuse and Alcoholism Grants K21AA00192 (A.H.N.) and AA08696 (R.J.H.) and by a Loyola University Neuroscience and Aging Institute Fellowship (A.H.N.). We thank Jennifer Dowd for her technical assistance.

    ☆☆

    Correspondence should be addressed to Alan H. Nagahara, Ph.D., Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80526. Fax: (970) 491-7907.

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