Helplessness and escape performance: glutamate-adenosine interactions in the frontal cortex.

Adenosine has been implicated as a proximate mediator of escape deficits in the learned helplessness paradigm, suggesting that neuronal overactivation-a typical precursor to adenosine release-precedes the inescapable shock-induced impairment (T. R. Minor, W. C. Chang, & J. L. Winslow, 1994). In the present experiments, glutamate (100 microg) injection into the rat frontal cortex produced a deficit in escape performance. Pretest treatment with the adenosine receptor antagonist caffeine (7 mg/kg ip) reversed the effect of glutamate when infused 1 hr. but not 72 hr, after glutamate injection. Finally, microinjection of 2-amino-5-phosphonovaleric acid (5 ng) into the frontal cortex prior to inescapable shock prevented the escape deficit. These findings are consistent with the involvement of N-methyl-D-aspartate receptor activation in the frontal cortex in the helplessness effect.