Exploring the neuroprotective potential of aprepitant against nicotine-induced molecular, histological, and behavioral sequels

Chronic nicotine exposure causes molecular and behavioral impairments. APRE, a selective NK1R antagonist, has neuroprotective potential. This study investigated whether APRE could protect against nicotine-induced neurotoxicity and mood- and motor-related behavioral changes in adult male Wistar rats. Forty-eight male Wistar rats were randomly assigned to six groups (n = 8) and treated intraperitoneally once daily for three weeks: group 1 received normal saline (0.5 mL/rat), group 2 received nicotine (10 mg/kg), groups 3–5 received nicotine (10 mg/kg) plus APRE (20, 40, or 80 mg/kg), and group 6 received APRE alone (80 mg/kg). Mood- and motor-related behaviors were assessed using OFT, EPM, and FST. In the hippocampus, mitochondrial function, oxidative stress, inflammation, apoptosis-related JNK/Bcl-2/Bax signaling, Beclin-1, and qualitative and quantitative histopathological changes in the DG and CA1 regions were investigated. APRE significantly attenuated nicotine-induced mood and motor disturbances. It also increased SOD, GPx, GR activity, TAC, ATP, MMP, GSH, and unphosphorylated Bcl-2, while reducing ROS, MDA, H2O2, GSSG, TNF-α, IL-1β, both forms of JNK, Bax, Beclin-1, and phosphorylated Bcl-2. In nicotine-exposed rats, APRE also significantly improved qualitative and quantitative histopathological changes in the DG and CA1 regions of the rat’s hippocampus. APRE mitigated multiple untoward effects of nicotine exposure, including behavioral disturbances, neuroinflammation, oxidative stress, cell death, and histopathological damage in the rat’s hippocampus.