Obvious anxiogenic-like effects of subchronic copper intoxication in rats, outcomes on spatial learning and memory and neuromodulatory potential of curcumin

Abstract

Copper (Cu) is a transition metal and an essential trace element, but excessive levels of Cu might disturb vital functions and systems including the Central Nervous System (CNS). Curcumin has numerous beneficial effects including protective potential on the CNS toxicity. Previous studies have revealed solid evidence showing metal elements implication in the physiopathology of psychiatric disorders, principally anxiety, as well as association between stressful conditions and the inception of anxiety. In addition, it was stated that stressful condition strengthens memory. The aim of the present study was to evaluate the influence of subchronic Cu-intoxication (0.125%) for 6 weeks on the serotonergic system and anxiety state along with spatial learning and memory performance, then test the therapeutic efficacy of curcumin I (30 mg/kg B.W.). In Cu-exposed rats, we noted a significant increased innervation of 5HT in dorsal raphe nucleus and Basolateral Amygdala (BLA) outputs; this was correlated with an anxiogenic-like effect in rats subjected to elevated plus-maze test. Curcumin co-treatment prevented Cu-induced anxiety and reversed 5-HT alterations. Cu did not alter learning and memory but main spatial learning and memory performance was remarked in treated rats with curcumin in Morris water maze. Results demonstrated that subchronic Cu intoxication induced an evident anxiogenic-like effect that was alleviated with curcumin treatment, then, impairment of monoamine neurotransmitters expression may be one of the major mechanisms implicated. Therefore, curcumin may be valuable in the treatment of anxiety disorders caused by metal elements by acting as an anxiolytic agent, and in the improvement of memory performance.