Acute restraint stress enhances calcium mobilization and glutamate exocytosis in cerebrocortical synaptosomes from mice.

Acute stress is known to enhance the memory of events that are potentially threatening to the organisms. Glutamate, the most abundant excitatory neurotransmitter in the mammalian central nervous system, plays a critical role in learning and memory formation and calcium (Ca(2+)) plays an essential role in transmitter release from nerve terminals (synaptosomes). In the present study, we investigated the effects of acute restraint stress on cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and glutamate release in cerebrocortical synaptosomes from mice. Acute restraint stress caused a significant increase in resting [Ca(2+)](i) and significantly enhanced the ability of the depolarizing agents K(+) and 4-aminopyridine (4-AP) to increase [Ca(2+)](i). It also brought about a significant increase in spontaneous (unstimulated) glutamate release and significantly enhanced K(+)- and 4-AP-induced Ca(2+)-dependent glutamate release. The pretreatment of synaptosomes with a combination of omega-agatoxin IVA (a P-type Ca(2+) channel blocker) and omega-conotoxin GVIA (an N-type Ca(2+) channel blocker) completely suppressed the enhancements of [Ca(2+)](i) and Ca(2+)-dependent glutamate release in acute restraint-stressed mice. These results indicate that acute restraint stress enhances K(+)- or 4-AP-induced glutamate release by increasing [Ca(2+)](i) via stimulation of Ca(2+) entry through P- and N-type Ca(2+) channels.