Hippocampal cholinergic alterations and related behavioral deficits after early exposure to ethanol

Abstract

The present study was designed to ascertain septohippocampal cholinergic alterations and their related behavioral deficits after early exposure to ethanol. Mouse pups were exposed to ethanol, 3 g/kg by daily subcutaneous injection on postnatal days 2-14. At age 50 days, the ethanol-exposed mice had significant reductions from control levels in eight-arm maze performance. For example, on the fourth testing day, the number of correct entries in the ethanol group was 21% below control levels (P < 0.05) and the number of trials needed to enter all arms was 48% above control (P < 0.001). It took the ethanol-exposed mice twice the time to reach criterion than it did control (P < 0.01). A 33% increase from control level in muscarinic receptor number (Bmax) was found in the treated mice of age 22 days and a 64% increase at age 50 days (P < 0.001). However, no differences between control and treated groups could be detected in the presynaptic component of the cholinergic innervation, choline acetyltransferase activity. The results suggest that early ethanol exposure acts on hippocampal function similarly to phenobarbital, probably via alterations in postsynaptic processes in the septohippocampal cholinergic pathways.

Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy

“…Only half of the alcohol-exposed offspring were able to reach criterion, and those that did required significantly more training trials relative to pair-fed controls. Pick et al (1993) reported similar effects in mice injected with ethanol (3 g/kg or 5 g/kg; sc) on PN2-14. At PN50, these mice took twice as many trials as controls to reach criterion, and continued to require significantly more trials than controls to enter all eight arms (Pick et al, 1993).…”

“…Pick et al (1993) reported similar effects in mice injected with ethanol (3 g/kg or 5 g/kg; sc) on PN2-14. At PN50, these mice took twice as many trials as controls to reach criterion, and continued to require significantly more trials than controls to enter all eight arms (Pick et al, 1993). Hall et al (1994) showed that midgestational alcohol exposure (i.e., gestational days (GD) 7-13), via 35% EDC liquid diets, was sufficient to impair radial maze acquisition when rats were tested as either juveniles (ϳPN26) or adults (ϳPN80).…”

Novel Molecular Targets for the Prevention of Fetal Alcohol Syndrome

“…Alcohol exposure alters cholinergic development and increases AChE and decreases acetylcholine transferase (AChT), diminishing the levels of ACh in cholinergic neurons [197][198][199][200][201]. Cognition is further compromised by the loss of cholinergic neurons [199]. Thus, it is reasonable to think that the expected augmentation of Ach available in the remaining cholinergic neurons, as a conesquence of ChEIs treatment, may improve FASD symptoms.…”

“…ChEIs block the catabolism of acetylcholine (ACh) by acetylcholinesterase (AChE), which leads to larger pool of available ACh to interact with postsynaptic ACh receptors and induce more lasting effects of this neurotransmitter during postnatal brain development. Alcohol exposure alters cholinergic development and increases AChE and decreases acetylcholine transferase (AChT), diminishing the levels of ACh in cholinergic neurons [197][198][199][200][201]. Cognition is further compromised by the loss of cholinergic neurons [199].…”

Early Postnatal Ethanol Exposure Has Long‐Term Effects on the Performance of Male Rats in a Delayed Matching‐to‐Place Task in the Morris Water Maze

“…Furthermore, DMTP versions of the water maze have shown deficits in rats with hippocampal and dentate gyrus (Steele and Morris, 1999) and fornix/fimbria lesions (Whishaw et al, 1995). Givenr that early postnatal ethanol exposure affects the development of the hippocampus (Bonthius and West, 1990;Greene et al, 1992;Pick et al, 1993), it is reasonable to expect that spatial DMTP-task performance would also be affected by ethanol. This is the first study to use this task to assess the effects of binge ethanol exposure during the brain growth spurt.…”