cholecystokinin and Stress-Disorders--Post-Traumatic

Cholecystokinin (CCK) is a neuropeptide that has been implicated in understanding the acquisition and extinction of fear. Research on CCK in anxiety has primarily focused on understanding panic attacks and panic disorder. Emerging data suggests that CCK may also hold promise in understanding the development and maintenance of posttraumatic stress disorder (PTSD).. The present study examined whether a single nucleotide polymorphism in the promoter region of the CCK gene (C>T; rs1799923) was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms among a sample of 457 combat veterans.. Results demonstrated that participants with either the heterozygous or homozygous T allele had an increased prevalence of PTSD relative to participants with the CC genotype (OR=2.17; 95% CI [1.37-3.43]).. The relatively small sample size precluded examination of racial/ethnic differences. Findings were also limited by the absence of a systematic assessment of comorbid anxiety psychopathology.. These data offer preliminary evidence supporting an association between the rs1799923 polymorphism in the CCK gene and PTSD. Additional research is needed to better understand the nature of this relationship.

Topics: Adult; Alleles; Anxiety Disorders; Cholecystokinin; Combat Disorders; Female; Genotype; Humans; Male; Middle Aged; Panic Disorder; Polymorphism, Genetic; Promoter Regions, Genetic; Stress Disorders, Post-Traumatic; Veterans

Post-traumatic stress disorder (PTSD), a debilitating psychiatric disease characterized by invasive and persistent fear memories-induced stressful experience, is associated with numerous changes in neuroendocrine function. Here, we investigated whether PTSD-like symptoms are associated with changes in the cholecystokinin (CCK) system in the basolateral amygdala. We developed an animal model of PTSD using multiple foot shocks at 1.1 mA. The resulting conditioned fear response was severe (>80% freezing) and maintained for at least 28 days. The stress-associated neurotransmitters norepinephrine, dopamine, and corticotrophin-releasing hormone were elevated at 1 day after foot shock. CCK immunoreactivity and extracellular concentration as well as the expression of CCK receptors (CCK1R, CCK2R) increased progressively for 28 days following foot shock. Taken together, these results suggest that stress-induced activation of the CCK system in the BLA, which may contribute toward the development of PTSD-like symptoms.

Topics: Amygdala; Animals; Cholecystokinin; Conditioning, Psychological; Corticotropin-Releasing Hormone; Disease Models, Animal; Dopamine; Electroshock; Extracellular Space; Fear; Foot; Freezing Reaction, Cataleptic; Male; Norepinephrine; Random Allocation; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Stress Disorders, Post-Traumatic; Time Factors

Topics: Animals; Anti-Anxiety Agents; Anxiety; Behavior, Animal; Benzamides; Cholecystokinin; Indoles; Male; Maze Learning; Meglumine; Odorants; Proglumide; Rats; Rats, Wistar; Receptors, Cholecystokinin; Stress Disorders, Post-Traumatic; Stress, Psychological