title: Stereological analyses of reward system nuclei in maternally deprived/separated alcohol drinking rats.
abstract: The experience of early life stress can trigger complex neurochemical cascades that influence emotional and addictive behaviors later in life in both adolescents and adults. Recent evidence suggests that excessive alcohol drinking and drug-seeking behavior, in general, are co-morbid with depressive-like behavior. Both behaviors are reported in humans exposed to early life adversity, and are prominent features recapitulated in animal models of early life stress (ELS) exposure. Currently, little is known about whether or how ELS modulates reward system nuclei. In this study we use operant conditioning of rats to show that the maternal separation stress (MS) model of ELS consumes up to 3-fold greater quantities of 10% vol/vol EtOH in 1-h, consistently over a 3-week period. This was correlated with a significant 22% reduction in the number of dopaminergic-like neurons in the VTA of naïve MS rats, similar to genetically alcohol-preferring (P) rats which show a 35% reduction in tyrosine hydroxylase (TH)-positive dopaminergic neurons in the VTA. MS rats had a significantly higher 2-fold immobility time in the forced swim test (FST) and reduced sucrose drinking compared to controls, indicative of depressive-like symptomology and anhedonia. Consistent with this finding, stereological analysis revealed that amygdala neurons were 25% greater in number at P70 following MS exposure. Our previous examination of the dentate gyrus of hippocampus, a region involved in encoding emotional memory, revealed fewer dentate gyrus neurons after MS, but we now report this reduction in neurons occurs without effect on the number of astrocytes or length of astrocytic fibers. These data indicate that MS animals exhibit neuroanatomical changes in reward centers similar to those reported for high alcohol drinking rats, but aspects of astrocyte morphometry remained unchanged. These data are of high relevance to understand the breadth of neuronal pathology that ensues in reward loci following ELS.
authors.affiliation: Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, United States; Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, United States. Electronic address: Mgondre-lewis@howard.edu.
authors.forename: Marjorie C
authors.initials: MC
authors.lastname: Gondré-Lewis
authors.affiliation: Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, United States; Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, United States.
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Darius
authors.affiliation: Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, United States.
authors.forename: Joanne S
authors.initials: JS
authors.lastname: Allard
keywords: Alcohol-preferring rats; Amygdala; Dentate gyrus; Drug addiction; Early life stress; Excessive alcohol drinking; Maternal deprivation; Maternal separation; P rats; Stereology; VTA