{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:51:41Z","timestamp":1792119101246,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T00:00:00Z","timestamp":1332115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hippocampus"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prenatal alcohol exposure leads to long\u2010lasting cognitive and attention deficits, as well as hyperactivity. Using a rat model, we have previously shown that perinatal supplementation with the essential nutrient, choline, can reduce the severity of some fetal alcohol effects, including hyperactivity and deficits in learning and memory. In fact, choline can mitigate alcohol\u2010related learning deficits even when administered after developmental alcohol exposure, during the postnatal period. However, it is not yet known how choline is able to mitigate alcohol\u2010related behavioral alterations. Choline may act by altering cholinergic signaling in the hippocampus. This study examined the effects of developmental alcohol exposure and perinatal choline supplementation on hippocampal M<jats:sub>1<\/jats:sub>and M<jats:sub>2\/4<\/jats:sub>muscarinic receptors. Sprague\u2010Dawley rat pups were orally intubated with ethanol (5.25 mg\/kg\/day) from postnatal days (PD) 4\u20139, a period of brain development equivalent to the human third trimester; control subjects received sham intubations. From PD 4\u201330, subjects were injected s.c. with choline chloride (100 mg\/kg\/day) or saline vehicle. Open field activity was assessed from PD 30 through 33, and brain tissue was collected on PD 35 for autoradiographic analysis. Ethanol\u2010exposed subjects were more active compared to controls during the first 2 days of testing, an effect attenuated with choline supplementation. Developmental alcohol exposure significantly decreased the density of muscarinic M<jats:sub>1<\/jats:sub>receptors in the dorsal hippocampus, an effect that was not altered by choline supplementation. In contrast, developmental alcohol exposure significantly increased M<jats:sub>2\/4<\/jats:sub>receptor density, an effect mitigated by choline supplementation. In fact, M<jats:sub>2\/4<\/jats:sub>receptor density of subjects exposed to alcohol and treated with choline did not differ significantly from that of controls. These data suggest that developmental alcohol exposure can cause long\u2010lasting changes in the hippocampal cholinergic system and that perinatal choline supplementation may attenuate alcohol\u2010related behavioral changes by influencing cholinergic systems. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22009","type":"journal-article","created":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T12:48:19Z","timestamp":1332161299000},"page":"1750-1757","source":"Crossref","is-referenced-by-count":81,"title":["The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt"],"prefix":"10.1002","volume":"22","author":[{"given":"Bradley R.","family":"Monk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer D.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.10035"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.450020407"},{"key":"e_1_2_5_4_1","unstructured":"BirdsallNJ BrownDA BuckleyNJ ChristopoulosA EglenRM EhlertFJ HammerR KilbingerHH GunterL FredM MutschleE NathansonNM SchwarzRD TobinAB WessJ.2010.Acetylcholine Receptors (muscarinic). 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