TEMPORAL DYNAMICS OF GLUTAMATE EFFLUX IN THE PREFRONTAL CORTEX AND INTHE HIPPOCAMPUS FOLLOWING REPEATED STRESS - EFFECTS OF PRETREATMENT WITH SALINE OR DIAZEPAM

Acute stress has been associated with activation of glutamate efflux i n forebrain structures. The present study sought to characterize the e xtracellular dynamics of glutamate in response to acute and repeated s tress in the prefrontal cortex and hippocampus in rats. One-minute sam pling of extracellular glutamate levels was performed during repeated tail-pinch stress. Animals were stressed three times, beginning at app roximately 10.30 a.m. and continuing at 2.5-h intervals. In the prefro ntal cortex, the initial 10-min tail pinch produced a robust increase in extracellular levels of glutamate. This increase was apparent immed iately (i.e. 1 min) after the start of the stress procedure. The secon d tail pinch produced a smaller increase in glutamate levels while the third tail pinch did not significantly increase these levels. In the hippocampus, the initial stress response was smaller in magnitude than that observed in the prefrontal carter. Furthermore, responses to sub sequent tail pinches were similar to that seen following the first tai l pinch. Treatment with diazepam (3 mg/kg i.p.) 30 min before the firs t stress session abolished the stress response in the prefrontal corte x and hippocampus. However, in the prefrontal cortex, the second tail pinch (performed approximately 3h after diazepam administration) produ ced a robust increase in glutamate efflux. In contrast, in the hippoca mpus of diazepam-treated rats, the second tail pinch produced a small delayed response. Pretreatment with saline resulted in non-significant responses to all three tail pinches in the prefrontal cortex. The pre sent study suggests that: (i) stress produces a rapid increase in glut amate efflux in the prefrontal cortex and hippocampus, (ii) repeated s tress reveals tolerance in the glutamatergic response in the prefronta l cortex, (iii) saline and diazepam pretreatment reduce the stress-ind uced efflux of glutamate in the prefrontal cortex, and (iv) exposure t o diazepam may prevent the prefrontal cortex from adapting its respons e to the subsequent stressor. These finding are consistent with the ro le of the prefrontal cortex as a region which may regulate reactions t o aversive stimuli. Copyright (C) 1997 IBRO.