PRESYNAPTIC ALTERATIONS ASSOCIATED WITH ENHANCEMENT OF EVOKED RELEASEAND SYNTHESIS OF NOREPINEPHRINE IN HIPPOCAMPUS OF CHRONICALLY COLD-STRESSED RATS

We have previously demonstrated that prior exposure to chronic cold st ress does not alter basal levels of norepinephrine (NE) release or syn thesis in hippocampus of rat. However, in response to a subsequent nov el stressor, an enhancement of both of these noradrenergic parameters is observed in the chronically stressed animals relative to naive cont rols. In the present experiments, we have examined whether the biochem ical sensitization of NE release and synthesis produced by chronic str ess can be demonstrated by local depolarization of the noradrenergic n erve terminals with elevated K+. The local application of elevated Kin dorsal hippocampus resulted in a greater increase in extracellular NE and 3,4-dihydroxyphenylacetic acid (DOPAC) in chronically stressed rats than in naive controls. It is proposed that in dorsal hippocampus , extracellular NE and DOPAC provide measures of NE release and biosyn thesis, respectively. Therefore, these data suggest that local depolar ization, similar to novel stress, elicits both enhanced NE release and synthesis in chronically stressed rats. One factor that is known to m odulate both of these processes is the presynaptic alpha-2 adrenergic receptor. Therefore, we examined whether a change in the sensitivity o f these receptors might contribute to the altered noradrenergic respon sivity observed in chronically stressed rats. Local administration of clonidine, an alpha-2 receptor agonist, produced a decrease in extrace llular NE and DOPAC in both naive and chronically stressed rats. The d ose-response curve for the effect of clonidine on NE was shifted to th e left in the latter group. In addition, local administration of idazo xan, an alpha-2 receptor antagonist, produced a greater increase in ex tracellular NE and DOPAC in the chronically stressed rats than in naiv e controls. These data suggest that an increase in the alpha-2 recepto r modulation of NE release and synthesis is operative in the chronical ly stressed animals. Although this apparent supersensitivity of the al pha-2 receptors cannot readily explain the enhancement of evoked norad renergic responses observed in chronically stressed rats, it may under lie the unaltered basal levels of NE release and synthesis observed in these animals.