Comorbidity of Post-Traumatic Stress Disorder and Alcohol Use Disorder: Animal Models and Associated Neurocircuitry

Abstract

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are prevalent neuropsychiatric disorders and frequently co-occur concomitantly. Individuals suffering from this dual diagnosis often exhibit increased symptom severity and poorer treatment outcomes than those with only one of these diseases. Lacking standard preclinical models limited the exploration of neurobiological mechanisms underlying PTSD and AUD comorbidity. In this review, we summarize well-accepted preclinical model paradigms and criteria for developing successful models of comorbidity. We also outline how PTSD and AUD affect each other bidirectionally in the nervous nuclei have been heatedly discussed recently. We hope to provide potential recommendations for future research.

Keywords: amygdala; animal model; comorbid PTSD and AUD; dopamine; hippocampus; locus coeruleus; mesolimbic reward circuit; paraventricular nuclei; the prefrontal cortex; ventral tegmental area.

Figure 1

The illustration of the predominant brain regions and circuits is generally thought to mediate the processing of reward (orange), HPA (red), and NE system (green) in the human brain. The NAc is usually the central node of reward circuits, including the DAe input from the VTA and excitatory input from other limbic structures. CRH from the hypothalamus stimulates ACTH release from the anterior pituitary into the bloodstream, then ACTH induces GCS release from the adrenal gland. GCS mediates negative feedback in the HPA axis to reduce the stress response. GCS also affects the circuitry via the GCS receptors, triggering molecular and cellular. The primary stress-related central NE system originates in the LC and plays an integral role in the comorbidity. Some of the many connections that link elements of the comorbidity are illustrated by black lines. LC, locus coeruleus; CRF, corticotropin-releasing factor; eCB, endocannabinoid; NP, neuropeptide; HPC, hippocampus; vmPFC, ventromedial prefrontal cortex; dlPFC, dorsolateral prefrontal cortex; AMY, amygdala; NAc, nucleus accumbens; VTA, ventral tegmental area; GCS, glucocorticoids; CRH, corticotropin-releasing hormone; ACTH, adrenocorticotrophic hormone; NE, norepinephrine.