Role of BLA kappa opioid receptors in adolescent anxiety and ethanol consumption

乙醇的使用在世界范围内是一种普遍现象，乙醇暴露的开始是一个主要问题

Ethanol use is a common occurrence worldwide, and the onset of ethanol exposure is a major contributing factor to ethanol abuse. Adolescence is a developmental period when ethanol use is typically initiated, making it a highly vulnerable time to predispose future abuse and alterations in neurobehavioral function. Moreover, adolescents consume more ethanol per drinking session than adults, perhaps due to the greater sensitivity to the anxiolytic properties of ethanol during this highly stressful and anxiety-provoking developmental stage. However, the neurobiological mechanisms of acute ethanol in adolescents are poorly understood. The opioid system is a major target of ethanol and kappa opioid receptors (KORs), particularly, have been shown to play a major role in the neurophysiological effects of ethanol in the reward and anxiety circuits. The basolateral amygdala (BLA), a key structure of the reward and anxiety circuits, is involved in ethanol-seeking behaviors. Specifically, alterations in GABA transmission within the BLA are associated with the anxiolytic properties of ethanol and ethanol-seeking. Importantly, KOR activation modulates BLA excitability and anxiety-like behaviors in an age-dependent manner, suggesting that KORs may significantly contribute to the increased sensitivity to the anxiolytic properties of ethanol in adolescents, which may drive increased ethanol consumption in adolescence. Thus, the overarching goal of this proposal is to test the interactions between BLA KORs and ethanol consumption in adolescents. Importantly, preliminary findings indicate that a KOR agonist potentiates GABAergic transmission within the BLA of adolescents, but not adults, and this effect is similar to that of acute ethanol. This suggests that ethanol may hijack the KOR system, thereby resulting in anxiolysis, which helps promote ethanol consumption in adolescents. Two Specific Aims will (1) determine the functional interactions between BLA KOR activation and acute ethanol in vitro and (2) examine the interaction of BLA KORs and acute ethanol on anxiety-like behavior and ethanol consumption. These innovative studies will test novel and unique hypotheses surrounding the developmental differences of ethanol and describe neural mechanisms specific to adolescent ethanol exposure.