Effect of Curcumin-Loaded Chitosan Nanoparticles and phenylalanine on Behavioral Performance and Brain Histology in Haloperidol-Treated Male Rats

Neurotoxicity from agents like heavy metals, pesticides, chemicals, and drugs disrupts neurotransmission and causes oxidative stress, leading to neuronal degeneration. This study tested the neuroprotective effects of curcumin-loaded chitosan nanoparticles and phenylalanine against haloperidol-induced neurotoxicity in male rats. Fifty healthy rats (3–4 months, 250–300 g) from Al-Qadisiyah University were divided into five groups (n=10). Group 1 was controls, receiving distilled water for 30 days. Groups 2–5 received haloperidol (2 mg/kg i.p.) for 14 days. Group 2 was positive control; Groups 3 and 4 received curcumin-chitosan nanoparticles (100 mg/kg) and phenylalanine (2 mg/kg), respectively; Group 5 received both for 30 days after haloperidol. Behavioral tests (Open Field, Y-Maze, Forced Swimming) were conducted. Brain tissues were examined after fixation. Haloperidol reduced locomotion, exploration, and memory, increasing immobility. Curcumin nanoparticles and phenylalanine improved behaviors; their combination nearly normalized activity. Histology showed neuronal contraction, pyknosis, chromatin fragmentation, vascular congestion, and gliosis, indicating severe neurotoxicity. Both treatments reduced these effects; the combination significantly restored neuronal structure and decreased necrosis and gliosis. In conclusion, combined curcumin-loaded chitosan nanoparticles and phenylalanine provided strong neuroprotection against haloperidol toxicity, enhancing activity and neuronal integrity.