Sex- and dose-dependent effects of post-trial calcium channel blockade by magnesium chloride on memory for inhibitory avoidance conditioning.

Calcium influx through voltage-dependent Ca(2+) channels is critical for many neuronal processes required for learning and memory. Persistent increases in cytosolic intracellular Ca(2+) concentrations in aging neurons are associated with learning impairments, while small transient subcellular changes in intracellular calcium concentrations play critical roles in neural plasticity in young neurons. In the present study, young male and female Fisher 344 × Brown Norway (FBN) hybrid rats were administered different doses of magnesium chloride (0.0, 100.0, or 200.0mg/kg, i.p.) following a single inhibitory avoidance training trial. Extracellular magnesium ions can non-specifically block voltage-gated calcium channels, and/or reduce the calcium conductance gated via glutamate and serine's activation of neuronal NMDA receptors. In our study, magnesium chloride dose-dependently enhanced memory compared to controls (significantly increased latency to enter a dark compartment previously paired with an aversive stimulus) when tested 48 h later as compared to controls. A leftward shift in the dose response curve for memory enhancement by magnesium chloride was observed for male compared to female rats. These findings provide further insights into calcium-dependent modulation of aversive memory, and should be considered when assessing the design of effective treatment options for both male and female patients with dementia or other memory problems.