Hypofunction of prefrontal cortex NMDA receptors does not change stress-induced release of dopamine and noradrenaline in amygdala but disrupts aversive memory.

RATIONALE: A dysfunction of prefrontal cortex has been associated with the exacerbated response to stress observed in schizophrenic patients and high-risk individuals to develop psychosis. The hypofunction of NMDA glutamatergic receptors induced by NMDA antagonists produces cortico-limbic hyperactivity, and this is used as an experimental model to resemble behavioural abnormalities observed in schizophrenia.
OBJECTIVES: The aim of the present study was to investigate whether injections of NMDA antagonists into the medial prefrontal cortex of the rat change (1) the increases of dopamine, noradrenaline and corticosterone concentrations produced by acute stress in amygdala, and (2) the acquisition of aversive memory related to a stressful event.
METHODS: Male Wistar rats were implanted with guide cannulae to perform microdialysis and bilateral microinjections (0.5 μl/side) of the NMDA antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phophonic acid (CPP) (25 and 100 ng). Prefrontal injections were performed 60 min before restraint stress in microdialysis experiments, or training (footshock; 0.6 mA, 2 s) in inhibitory avoidance test. Retention latency was evaluated 24 h after training as an index of aversive memory.
RESULTS: Acute stress increased amygdala dialysate concentrations of dopamine (160% of baseline), noradrenaline (145% of baseline) and corticosterone (170% of baseline). Prefrontal injections of CPP did not change the increases of dopamine, noradrenaline or corticosterone produced by stress. In contrast, CPP significantly reduced the retention latency in the inhibitory avoidance test.
CONCLUSIONS: These results suggest that the hypofunction of prefrontal NMDA receptors does not change the sensitivity to acute stress of dopamine and noradrenaline projections to amygdala but impairs the acquisition of aversive memory.