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β ‐Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety‐Like Behaviors in Prenatal Alcohol‐Exposed Rats and Alcohol‐Non‐Preferring and Alcohol‐Preferring Rats
Author(s) -
Logan Ryan W.,
Wynne Olivia,
Maglakelidze George,
Zhang Changqing,
O'Connell Stephanie,
Boyadjieva Nadka I.,
Sarkar Dipak K.
Publication year - 2015
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12611
Subject(s) - corticosterone , hypothalamus , endocrinology , amygdala , medicine , elevated plus maze , anxiety , alcohol , central nucleus of the amygdala , maternal deprivation , psychology , chemistry , psychiatry , hormone , biochemistry
Background Alcohol exposure has adverse effects on stress physiology and behavioral reactivity. This is suggested to be due, in part, to the effect of alcohol on β ‐endorphin ( β ‐ EP )‐producing neurons in the hypothalamus. In response to stress, β ‐ EP normally provides negative feedback to the hypothalamic–pituitary–adrenal axis and interacts with other neurotransmitter systems in the amygdala to regulate behavior. We examined whether β ‐ EP neuronal function in the hypothalamus reduces the corticosterone response to acute stress, attenuates anxiety‐like behaviors, and modulates alcohol drinking in rats. Methods To determine whether β ‐ EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated β ‐ EP neurons into the paraventricular nucleus (PVN) of the hypothalamus of normal, prenatal alcohol‐exposed, and alcohol‐preferring (P) and alcohol‐non‐preferring ( NP ) rats. We then assessed corticosterone levels in response to acute restraint stress and other markers of stress response in the brain and anxiety‐like behaviors in the elevated plus maze and open‐field assays. Results We showed that β ‐ EP neuronal transplants into the PVN reduced the peripheral corticosterone response to acute stress and attenuated anxiety‐like behaviors. Similar transplants completely reduced the hypercorticosterone response and elevated anxiety behaviors in prenatal alcohol‐exposed adult rats. Moreover, we showed that β ‐ EP reduced anxiety behavior in P rats with minimal effects on alcohol drinking during and following restraint stress. Conclusions These data further establish a role of β ‐ EP neurons in the hypothalamus for regulating physiological stress response and anxiety behavior and resemble a potential novel therapy for treating stress‐related psychiatric disorders in prenatal alcohol‐exposed children and those genetically predisposed to increased alcohol consumption.