Abstract
When the rats are exposed to immobilization stress, these rats reveal not only the negative emotional responses such as vocalization and defecation which are considered to be similar to anxiety and/or fear in humans but also increases in noradrenaline release in the extended brain regions including the hypothalamus, amygdala and locus coeruleus. These stress-induced increases in noradrenaline release in these brain regions and emotional responses were significantly attenuated by pretreatment with diazepam, a typical benzodiazepine anxiolytic, in a flumazenil, a benzodiazepine antagonist, reversible manner. Similarly, morphine and opioid peptides injected i.c.v. such as β-endorphin and Met-enkephalin also significantly attenuated stress-induced increases in noradrenaline release in these region and emotional responses in a naloxone, an opoiod antagonist, reversible manner. When both diazepam at 5 mg/kg and morphine at 6 mg/kg were administered immediately before exposure to immobilization stress for 1 h, these two drugs showed the more potent attenuating effects on stress-induced increases in noradrenaline release in these brain regions than those caued by diazepam or morphine alone. The finding suggsets that if the drug possessing affinity to both benzodiazepine and opioid receptors were discovered, the drug could be a more potent anxiolytic than benzodiazepine anxiolytics. Further, we examined the involvement of corticotropin-releasing factor (CRF) in the stress-induced increases in brain noradrenaline release. When the rast were pretreated with a-helical CRF, an antagonist of CRF, stress-induced increases in noradrenaline release in the hypothalamus, amygdala and locus coeruleus were significantly attenuated by α-helical CRF. This indicates that CRF, at least, in part, has an important role for the initiation of increases in noradrenaloine release caused by stress in the extended brain regions. The finding suggests another possibility that a CRF-antagonist could be a useful anxiolytic and or anti-stress drug.
