The role of peripheral cardiovascular signals in the interoceptive effects of alcohol

点击翻译按钮获取中文摘要

Abstract Interoception is the process of sensing and integrating internal signals, which is critical for maintaining bodily homeostasis. Interoceptive signals such as hunger, thirst, or arousal can thus impact behavior. Alcohol, as well as all other drugs of abuse, produces distinct interoceptive effects (i.e., lightheadedness, dizziness, relaxation). These interoceptive effects can vary dramatically by dose. Given the rich conditioning history one experiences between alcohol drinking and the interoceptive effects associated with drinking, it is important to consider that these effects could have the potential to influence drinking (signaling satiety or priming more drinking). While advances have been made in our understanding of the CNS neural circuitry and molecular mechanisms that modulate the expression of alcohol interoceptive effects, little is known regarding the role of peripheral cues to these interoceptive effects. Afferent signals from the cardiovascular system are one of the major sources of interoceptive information and as such perception of cardiac activity is a salient and central feature of interoception. To this end the goal of this application is 1) to characterize the role of peripheral cardiovascular information (heart rate and blood pressure) in the expression of the interoceptive effects of low and moderate/high alcohol doses, and 2) the functional role of the nucleus of the solitary tract (NTS), a primary brainstem target of visceral afferents in the integration of cardiovascular signals underlying alcohol interoceptive sensitivity. One of the NTS efferent targets is the nucleus reuniens (Re), a basal midline thalamic nucleus that has been relatively understudied in its role in interoception. In Aim 1, studies will assess cardiovascular signals across alcohol interoceptive training and take a pharmacological approach to directly test the functional involvement of peripheral cardiovascular signals to alcohol interoceptive effects. Studies in Aim 2 will assess the functional role of the NTS and the NTSnucleus reuniens (Re) pathway in alcohol effects and as a critical component of these cardiovascular signals. The results of the proposed studies will provide new insight into our understanding of alcohol interoceptive effects and would be the first preclinical studies to characterize peripheral cardiovascular signals in the interoceptive stimulus effects of alcohol. These findings will have broad relevance for improving our understanding of interoceptive processing and the interplay between peripheral changes and motivated behavior that is guided by alcohol interoceptive effects.