Repeated caffeine administration aggravates post-traumatic stress disorder-like symptoms in rats.

Caffeine is the widely consumed central nervous system stimulant in form of coffee and other beverages. However, the repeated administration of caffeine induces anxiety, disturbance in hypothalamic-pituitary-adrenal (HPA) axis and psychiatric symptoms in humans. As much evidence links PTSD to HPA axis dysfunction, and anxiety is a hallmark symptom, repeated and/or large doses of caffeine may exacerbate symptoms of PTSD. In our present study, we evaluated the effect of repeated administration of caffeine on stress re-stress (SRS) model of PTSD. As per the protocol, male rats were restrained for 2 h followed by 20 min forced swim and halothane anaesthesia on day 2 (D-2). Then the rats were re-stressed (forced swim) at 6-days interval between D-8 to D-32. After exposure to SRS, depressive, anxiety-like behaviour, and cognitive functions were evaluated by forced swim test (FST), elevated plus maze (EPM) and Y-maze tests respectively. Caffeine (10, 20 and 30 mg/kg, i.p.) dosing was started from D-8 and continued up to D-32. The corticosterone level was measured in plasma followed by serotonin and glucocorticoid receptor (GR) and mineralocorticoid receptors (MR) estimation in hippocampus (HIP), prefrontal cortex (PFC) and amygdala (AMY). SRS-induced depressive and anxiety-like behaviour was aggravated by caffeine at dose of 20 and 30 mg/kg. Caffeine (30 mg/kg) treated control animals showed depressive, anxiety-like behaviour and cognitive impairments. SRS-induced decrease in plasma corticosterone level and increase in serotonin (5HT) levels in the PFC, HIP and AMY were not altered by caffeine. Caffeine did not modulate the SRS-induced decrease in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). In contrast, caffeine per se decreased GR and MR expression and their ratio in unstressed animals. Repeated intake of caffeine aggravates PTSD-like symptoms in stress-exposed rats and induces PTSD-like symptoms in unstressed rats by altering the expression of glucocorticoid receptors. Unlabelled Image • SRS-induced PTSD-like behaviour was aggravated by caffeine. • Repeated administration of caffeine caused PTSD-like effect in unstressed rats. • Caffeine does not modulate SRS-induced decrease in plasma corticosterone. • SRS-induced increase in 5-HT levels remain unaltered by caffeine. • SRS-induced decrease in MR and GR receptor expression remain unchanged by caffeine. [ABSTRACT FROM AUTHOR]