Binge neonatal alcohol intubations induce dose-dependent loss of Purkinje cells.
Previous work using artificial rearing methods to administer alcohol to neonatal rats identified postnatal days (PD) 4-6 as a period of enhanced vulnerability to alcohol-induced Purkinje cell loss. To develop an alternative to artificial rearing, alcohol was administered to pups in a binge pattern of exposure using acute intubations, and dose-related effects on blood alcohol concentrations (BACs), somatic growth, and cerebellar Purkinje cell survival were assessed. Pups were intubated with alcohol in milk formula, twice a day, 2 h apart, with total daily doses of 4.5, 5.25, or 6.0 g/kg of alcohol. After intubations on PD 4, the blood alcohol concentration (BAC)-time curves systematically increased with increasing dose. Intubation of these doses on PD 4-6 produced significant, dose-dependent reductions in the total number of cerebellar Purkinje cells on PD 10, counted using the stereological optical fractionator. Somatic growth was significantly affected only by the highest dose. These dose manipulations using intubations confirmed that Purkinje cell death systematically increased as a function of BAC profiles within the PD 4-6 window of vulnerability.
Goodlett
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CR
Department of Psychology, Indiana University-Purdue University at Indianapolis 46202-3275, USA. cgoodlet@iupui.edu
Pearlman
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Lundahl
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D000428:Alcohol Drinking / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007441:Intubation, Gastrointestinal; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley