DIFFERENTIAL-EFFECTS OF RESTRAINT STRESS ON HIPPOCAMPAL 5-HT METABOLISM AND EXTRACELLULAR LEVELS OF 5-HT IN STREPTOZOTOCIN-DIABETIC RATS

Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hy droxytryptamine, 5-HT) synthesis/metabolism, but whether this reductio n leads to decreased release of 5-HT has only scarcely been investigat ed. We have thus analysed the impact of STZ diabetes on hippocampal ex tracellular 5-HT levels both under basal conditions and during restrai nt stress, a procedure known to stimulate hippocampal 5-HT synthesis/m etabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hip pocampal 5-HT metabolism, as assessed by I:issue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialys is revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle-and STZ-pretreated rats, but a differential ef fect of restraint. Thus, extracellular 5-HT levels increased throughou t restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretr eated rats. In the latter rat group, plasma corticosterone levels were , however, increased, thus indicating a significant aversiveness to st ress. Lastly, because anxiety-related behaviours may be affected by hi ppocampal serotonergic systems, resting and restrained vehicle-and STZ -pretreated rats were compared (immediately after stress) in an elevat ed plus-maze of anxiety. Pretreatment with STZ reduced the percent num ber of open arm entries and the number of closed arm entries, indicati ng increased anxiety and reduced locomotor activity, respectively. Res traint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering a ffective disorders could be related to the lack of hippocampal seroton ergic response to aversive stimuli. (C) 1997 Elsevier Science B.V.