The Effects of Alcohol Exposure on a Cerebellar Functioning Task in Rats and the Neuroprotective Effects of Agmatine: A Third Trimester Model

Institution

University of Kentucky

Abstract

This study investigated the effects of neonatal alcohol exposure on a balance task that relies on cerebellar function. This exposure period was selected because it closely resembles central nervous system development during the human third trimester of pregnancy. The cerebellum experiences considerable growth during this period and thus alcohol may have some of its most detrimental behavioral effects at this time. One hypothesis for alcohol’s effects on the developing brain is that neurons become overexcited during withdrawal and die. Some drugs are thought to protect the brain during alcohol withdrawal, one of which is agmatine sulfate. The hypothesis was that neonatal alcohol exposure would lead to deficits in cerebellar task performance and that agmatine would help reduce these deficits. Male and female rat pups were administered either alcohol, agmatine, an isocaloric control, or a combination of alcohol and agmatine, twice daily during postnatal days 4 through 9. At 19 days of age, animals had to walk and balance on two parallel rods. There were ten subjects per sex and treatment condition. With each successful trial, the distance between the bars was widened. Animals were tested three trials per day for three days. Alcohol exposed animals performed more poorly than all other treatment groups. Furthermore, animals neonatally exposed to the combination of alcohol and agmatine performed better than those exposed only to alcohol. This suggests that agmatine may have some utility as a neuroprotective agent for cerebellar damage due to neonatal alcohol exposure, but more research is needed.

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The Effects of Alcohol Exposure on a Cerebellar Functioning Task in Rats and the Neuroprotective Effects of Agmatine: A Third Trimester Model

This study investigated the effects of neonatal alcohol exposure on a balance task that relies on cerebellar function. This exposure period was selected because it closely resembles central nervous system development during the human third trimester of pregnancy. The cerebellum experiences considerable growth during this period and thus alcohol may have some of its most detrimental behavioral effects at this time. One hypothesis for alcohol’s effects on the developing brain is that neurons become overexcited during withdrawal and die. Some drugs are thought to protect the brain during alcohol withdrawal, one of which is agmatine sulfate. The hypothesis was that neonatal alcohol exposure would lead to deficits in cerebellar task performance and that agmatine would help reduce these deficits. Male and female rat pups were administered either alcohol, agmatine, an isocaloric control, or a combination of alcohol and agmatine, twice daily during postnatal days 4 through 9. At 19 days of age, animals had to walk and balance on two parallel rods. There were ten subjects per sex and treatment condition. With each successful trial, the distance between the bars was widened. Animals were tested three trials per day for three days. Alcohol exposed animals performed more poorly than all other treatment groups. Furthermore, animals neonatally exposed to the combination of alcohol and agmatine performed better than those exposed only to alcohol. This suggests that agmatine may have some utility as a neuroprotective agent for cerebellar damage due to neonatal alcohol exposure, but more research is needed.