Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model

Abstract

AbstractThe present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m‐amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m‐amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)‐1β, IL‐6, IL‐10, tumour necrosis factor‐α, dopamine‐cAMP‐regulated phosphoprotein of 32,000 kDa (DARPP‐32) and neuronal calcium sensor (NCS‐1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain‐derived neurotrophic factor (BDNF), neuronal growth factor and glial‐derived neurotrophic factor levels were assessed in the hippocampus. M‐amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m‐amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk‐like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m‐amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M‐amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M‐amphetamine dose‐dependently increased DARPP‐32 and NCS‐1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.