The Effect of Yoga on Cancer-Related Fatigue and Quality of Life Among Racially and Ethnically Diverse Cancer Survivors: A Secondary Data Analysis.

Alcohol is the most used addictive substance in the United States , with close to 29 million people aged 12 and older suffering from alcohol use disorder (AUD) in the past year . Alcohol use disorder is a chronic relapsing disease defined by compulsive seeking and consumption of alcohol, loss of control in limiting intake, and negative affective withdrawal syndrome also known as hyperkatifeia . In preclinical models, the transition to alcohol dependence involves chronic activation of brain stress systems which leads to the negative affective states seen in withdrawal, and negative reinforcement of these states compels further drinking . The extended amygdala is a brain macrostructure involved in AUD and encompasses numerous interconnected stress-related neuropeptidergic systems . The central amygdala (CeA), part of the extended amygdala, plays a central role in physiological responses to stressful and drug-related stimuli such as alcohol . The CeA is primarily gamma-aminobutyric acid (GABA)-ergic, and increased GABA release in the CeA is a hallmark of alcohol dependence in male rats , mice , and nonhuman primates . Chronic alcohol exposure leads to dysregulated GABA and glutamatergic signaling in the CeA, and this dysregulation is thought to be a significant contributor to the transition to alcohol dependence . The CeA contains many stress-related neuropeptide systems that modulate synaptic activity, such as the putative anti-stress peptide oxytocin and the pro-stress peptide corticotropin-releasing factor (CRF) Oxytocin receptors are found in many brain regions relevant to alcohol dependence, such as the extended amygdala, in rats and humans . Previously, we reported that oxytocin decreased evoked CeA GABA transmission in non-dependent rats and reduced the amplitude of spontaneous inhibitory GABAergic currents in both non-dependent and alcohol-dependent male rats8. In addition, oxytocin blocked the facilitatory effects of acute alcohol on GABA release in the CeA of dependent rats . Sex differences in synaptic transmission, at both presynaptic and postsynaptic sites, in the CeA of naive and alcohol-dependent rats have also been observed . We showed that spontaneous inhibitory postsynaptic current (sIPSC) kinetics differ between females and males, with naïve females having the fastest current kinetics . In addition, the increase in sIPSC frequency routinely found in males after acute alcohol administration was not observed in naïve females, and a physiologically high concentration of ethanol was required to significantly increase dependent female sIPSC frequencies . However, an electrophysiological characterization of oxytocin’s effects in alcohol-naive and alcohol-dependent female rats remains lacking. Given our previous findings of sex differences in alcohol-related neuroadaptations, we were particularly interested in determining whether similar oxytocin-mediated electrophysiological patterns would be observed in the CeM of females. Oxytocin receptor-expressing neurons are known to co-express CRF , and CRF is locally produced and released by neurons within multiple brain regions, including the CeA . The counteracting relationship between oxytocin and CRF in the CeA and its implication in alcohol dependence is not fully understood. Thus, we sought to elucidate the sex-specific effects of oxytocin on the development of alcohol dependence. Herein, we examined the electrophysiological effects of oxytocin and alcohol on CeA GABAergic transmission in both alcohol-naive and alcohol-dependent female rats.