[beta]-Endorphin Neuronal Transplantation Into the Hypothalamus Alters Anxiety-Like Behaviors in Prenatal Alcohol-Exposed Rats and Alcohol-Non-Preferring and Alcohol-Preferring Rats

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2015-01, Vol.39 (1), p.146
• Main Authors: Logan, Ryan W, Wynne, Olivia, Maglakelidze, George, Zhang, Changqing, O'Connell, Stephanie, Boyadjieva, Nadka I, Sarkar, Dipak K
• Format: Article
• Language: English
• Subjects: Alcohol; Anxiety; Behavior; Pituitary gland; Rodents; Stress; Stress response
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.12611

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 [beta]-endorphin ([beta]-EP)-producing neurons in the hypothalamus. In response to stress, [beta]-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 [beta]-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 [beta]-EP neuronal transplants modulate the stress response, anxiety behavior, and alcohol drinking, we implanted differentiated [beta]-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 [beta]-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 [beta]-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 [beta]-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.