The influence of serotonin depletion on rat behavior in the Vogel test andbrain H-3-zolpidem binding

'The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpid em's the behavioral effects and binding to some brain areas of zolpidem, wa s examined with the help of Vogel's punished drinking test and autoradiogra phy, respectively. Moreover, changes in the serotonin levels and turnover r ate were studied in the forebrain and brainstem of rats pretreated with var ious ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to s ignificantly disinhibit animal behavior suppressed by punishment in the Vog el test (Nazar et al., 1997). It was found that serotonin decrease in the f rontal cortex and hippocampus after p-CPA significantly and inversely corre lated with rat behavior controlled by fear in the VT. p-CPA produced an ant iconflict activity in the absence of effect on spontaneous drinking, pain t hreshold and motility of animals. All applied benzodiazepine receptor ligan ds decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyin doleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletio n in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all non-selective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seeme d to produce the same anticonflict effect and decreasing 5-HT turnover indi cates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, it was f ound that serotonin decrease enhanced the anticonflict effect of zolpidem i n the Vogel test and increased H-3-zolpidem binding to the occipital cortex and substantia nigra. Altogether, the present study provides more argument s for the role of changes in the activity of brain 5-HT innervation in the control of emotional processes. Moreover, it points to the BDZ(1) receptor subtype as a possible target of interaction between brain 5-HT and GABA(A)/ BDZ systems.