Alterations in hippocampal calcineurin protein levels are associated with the impairing effects of nandrolone on dorsal and ventral hippocampus-dependent memory in rats.

BACKGROUND: Nandrolone decanoate (ND) exposure has been associated with impairments in hippocampal-dependent learning and memory, potentially involving alterations in intracellular calcium signaling and Calcineurin protein expression. Given the distinct functional contributions of the dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) to cognitive and emotional processes, this study investigated whether ND-induced behavioral changes are associated with alterations in Calcineurin protein levels in these hippocampal subregions. MATERIALS AND METHODS: Twenty-seven male rats were randomly assigned to three groups (n = 9 per group) and received intraperitoneal injections of ND (5 or 15 mg/kg) or sesame oil as the vehicle control every third day for 22 days. Behavioral assessments included the Morris water maze (MWM) for spatial learning and memory, the open field test (OFT) for locomotor activity and anxiety-like behavior, and the passive avoidance test (PAT) for aversive memory. Following completion of behavioral testing, the animals were deeply anesthetized, and the brains were removed. The hippocampus was dissected from the right hemisphere and further separated into dorsal and ventral regions according to standard stereotaxic coordinates relative to Bregma. Tissue samples were homogenized, and Calcineurin protein levels in the dHPC and vHPC were quantified using a commercial ELISA kit according to the manufacturer's instructions. RESULTS: ND administration impaired both spatial and avoidance memory and was associated with increased Calcineurin protein levels in the dHPC and vHPC. These findings suggest an association between increased Calcineurin protein levels and Nandrolone-induced cognitive deficits in both hippocampal subregions. Additionally, Nandrolone did not significantly alter locomotor activity but reduced anxiety-like behavior in rats. CONCLUSIONS: These findings suggest that ND-associated learning and memory impairments are accompanied by alterations in Calcineurin protein levels in both the dHPC and vHPC. The region-dependent effects of ND on Calcineurin may contribute to the differential vulnerability of hippocampal subregions to ND exposure and provide further insight into the potential molecular mechanisms underlying the cognitive effects of anabolic-androgenic steroid exposure.