Since its inception in 2002, INIAstress has had the primary goal of coordinating and facilitating translational, multidisciplinary and integrative research aimed at elucidating genetic and environmental influences on brain mechanisms that mediate excessive alcohol (ethanol) consumption, the response to stress, and the reciprocal relationship between excessive drinking, the physiological state of stress, and the subjective state of anxiety. Through this characterization we have helped to define factors that contribute to an individual's risk for the development of alcoholism, revealed underlying mechanisms and conditions that promote excessive and harmful drinking, and forged progress towards discovering novel, more effective, and tailored treatment strategies. In the next renewal, the general goals of INIAstress Consortium are to (1) Elucidate the changes in brain circuitry to understand the molecular, cellular and synaptic mechanisms that underlie transition from regulated (social) drinking to excessive (addictive) drinking and (2) Elucidate changes in brain circuitry and mechanisms that underlie how alcohol alters response to stress, which in turn can facilitate the transition from regulated (non-addictive) drinking to excessive and habitual drinking.

As a collection of projects and cores, INIAstress provides the resources to address these main hypotheses:
1. Chronic ethanol exposure produces a process of allostasis that is characterized by dysregulation of the HPA axis activity, revealed during periods of abstinence or exposure to other stressors, and can synergistically promote further excessive intake of ethanol.
2. Chronic ethanol exposure produces adaptive changes in brain circuitry that are fundamental to an allostatic process characterized by functional alterations in neural circuitry of extrahypothalamic, corticostriatal and hypothalamic (prefrontal cortex, amygdala, the bed nucleus of the stria terminalis (BNST), dorsal striatum and ventral striatum (nucleus accumbens), and brainstem locus corelius. Allostatic changes in this circuitry are hypothesized to contribute to the promotion and perpetuation of excessive ethanol drinking.
3. Changes in endocrine activity help define ethanol allostasis and represent a translational link that mediates physiological and motivational consequences of altered stress responsiveness, anxiety, and escalation of drinking following chronic ethanol exposure.

To address these hypotheses the consortium will:
• Incorporate technically advanced approaches to increase our understanding of how the CNS adapts to chronic alcohol exposure in some individuals to increase alcohol intake and render them more susceptible to stressful events, which may, in turn, promote continued excessive drinking.
• Provide cross-species translational information that will fundamentally alter our knowledge of adaptations corresponding to the alcohol addiction process and the manner in which such adaptations influence stress interactions with alcohol.
• Integrate this information to provide novel and valuable insights that will inform diagnostic and prevention efforts as well as individualized treatment options for those suffering with alcohol use disorder (AUD) and co-morbidity with stress-related disorders such as post-traumatic stress disorders.

Collectively, these collaborative studies directly integrate behavioral, endocrine, neural and genetic data from animal models to humans within a scope of expertise and thematic inquiry that would not be possible using more traditional grant mechanisms.