Peptidergic mechanisms of resistance to behaviorally evoked emotional stress

Abstract

Under the various stressful situations, i t has been well known that the monoaminergic neuronal systems including noradrenaline (NA), dopamine (DA) and serotonin (5-hydroxytryptamine, 5-HT) are activated in the extended brain regions of the rodents. Based upon the previous experimental findings, we have proposed the hypothesis on anxiety that increases in NA release in such brain regions as the hypothalamus, amygdala and locus coeruleus are, in part, closed related to the provocation of anxiety and/or fear in animals exposed to stress. Moreover, we have suggested that anxiolyt ic drugs of benzodiazepines act to attenuate stress-induced increases in NA release in these regions, which results in the re l ie f of anxiety and/or fear. Recently, intracerebral microdialysis methods have been ut i l ized in the f ie ld of neurochemistry. In the present studies, we have investigated the effect of emotional stresses on neurotransmitter release such as NA, DA and 5-HT in the rat brain regions using in vivo microdialysis. Male Wistar rats weighing 200-300 g were used. The rats were anesthetized by pentobarbital and the microdialysis probe was inserted into one of the anterior hypothalamus, basolateral nucleus of the amygdala, medial prefrontal cortex, etc.. Perfusion was started 24 hrs after the operation with the flow rate of 2.5 ~I/min. One of NA, DA or 5-HT was determined by HPLC with ECD. Immobilization stress caused signif icant increases in extracelluar NA contents in the perfusates from the anterior hypothalamus and these increases were s igni f icant ly attenuated by diazepam, an anxiolyt ic of benzodiazepines in a flumazenil (an antagonist of benzodiazepines) reversible manner. The same stress increased NA contents from the basolateral nucleus of the amygdala and DA contents from the medial prefrontal cortex but neither from the nucleus accumbens nor from the caudate nucleus. Conditioned fear, wherein the rats were reexposed to the shock box without shock where they had received electr ic shock previously, caused increases in NA contents in the perfusate from the anterior hypothalamus. Psychological stress, wherein the rats were never shocked but exposed to the emotional responses shown by other electrically-shocked rats, increased 5-HT release in the medial prefrontal cortex and the basolateral nucleus of the amygdala. These findings further support our NA hypothesis on anxiety, however, involvements of other brain regions such as the medial prefrontal cortex and other monoamnergic systems including DA and 5-HT systems, are also important for the provocation of anxiety and/or fear.