title: The effects of postnatal alcohol exposure and galantamine on the context pre-exposure facilitation effect and acetylcholine efflux using in vivo microdialysis.
abstract: Fetal alcohol spectrum disorders (FASD) are characterized by damage to multiple brain regions, including the hippocampus, which is involved in learning and memory. The acetylcholine neurotransmitter system provides major input to the hippocampus and is a possible target of developmental alcohol exposure. Alcohol (3.0 g/kg/day) was administered via intubation to male rat pups (postnatal day [PD] 2-10; ethanol-treated [ET]). Controls received a sham intubation (IC) or no treatment (NC). Acetylcholine efflux was measured using in vivo microdialysis (PD 32-35). ET animals were not different at baseline, but had decreased K(+)/Ca(2+)-induced acetylcholine efflux compared to NC animals and an enhanced acetylcholine response to galantamine (acetylcholinesterase inhibitor; 2.0 mg/kg) compared to both control groups. A separate cohort of animals was tested in the context pre-exposure facilitation effect task (CPFE; PD 30-32) following postnatal alcohol exposure and administration of galantamine (2.0 mg/kg; PD 11-30). Neither chronic galantamine nor postnatal alcohol exposure influenced performance in the CPFE task. Using immunohistochemistry, we found that neither alcohol exposure nor behavioral testing significantly altered the density of vesicular acetylcholine transporter or alpha7 nicotinic acetylcholine receptor in the ventral hippocampus (CA1). In the medial septum, the average number of choline acetyltransferase (ChAT+) cells was increased in ET animals that displayed the context-shock association; there were no changes in IC and NC animals that learned the context-shock association or in any animals that were in the control task that entailed no learning. Taken together, these results indicate that the hippocampal acetylcholine system is significantly disrupted under conditions of pharmacological manipulations (e.g., galantamine) in alcohol-exposed animals. Furthermore, ChAT was up‑regulated in ET animals that learned the CPFE, which may account for their ability to perform this task. In sum, developmental alcohol exposure may disrupt learning and memory in adolescence via a cholinergic mechanism.
authors.affiliation: Department of Psychology, University of South Carolina, 1512 Pendleton St., Columbia, SC 29208, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Perkins
authors.affiliation: Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
authors.forename: Jim R
authors.initials: JR
authors.lastname: Fadel
authors.affiliation: Department of Psychology, University of South Carolina, 1512 Pendleton St., Columbia, SC 29208, USA; Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA. Electronic address: sandra-kelly@sc.edu.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Kelly
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D005239:Fear; D005702:Galantamine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D002492:Central Nervous System Depressants; D002800:Cholinesterase Inhibitors; D005702:Galantamine; D000431:Ethanol; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Context pre-exposure facilitation effect; Fetal alcohol spectrum disorder; Galantamine; In vivo microdialysis
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