The Effects of Repeated Stress on the GABAergic Neurotransmission in Rats / 신경정신의학

OBJECTIVES: Changes of GABAergic neurotransmission in response to the application of different types of environmental stress have been the subject of research for over two decades. However, the nature of the changes induced by stress appear to show a dependent phenomena on the type and duration of stressor agent employed. METHODS: For this reason, this study was performed to observe the effects of repeated stress on the radioligands binding to GABA A/benzodiazepine receptors of discrete brain regions. The author also examined the activity of GABA transaminase and the concentration of endogenous GABA. Male Sprague-Dawley rats, weighing 150-200g were forced to suffer an immobilization stress for 2 hours during 14 consecutive days. RESULTS: Repeated immobilization stress decreased the binding of [3H]flunitrazepam on the benzodiazepine receptor in the cortex, hippocampus and hypothalamus. Saturation experiments followed by scatchard analyses of the results showed decreased density of benzodiazepine receptor and the affinity remained unchanged. Repeated immobilization stress did not affect the binding of [3H]muscimol on the GABAA receptor, the activity of GABA transaminase, and the concentration of endogenous GABA in the brain regions. CONCLUSIONS: From these results, it can be concluded that repeated immobilization stress modulated GABAergic neurotransmission via downregulation of the benzodiazepine receptor in the brain.

The Effects of Repeated Stress on the Opioidergic Neurotransmission in Rats / 신경정신의학

OBJECTIVES: Research into emotional or behavioral stress typically focuses upon the hypothalamic-pituitary-adrenal axis. It is well established that the hypothalamic-pituitary-adrenocortical axis is subject to inhibitory control by opioids in a variety of animal species including pigs. Exposure to acute stress induces the upregulation of opioid receptors and the release of endogenous peptides which mediate the stress-induced analgesia. There is some literature substantiating that repeated stress can lead to changes in opioidergic neurotransmission. However, the changes are highly variable. This study was designed to observe the modulatory effect of repeated immobilization stress on opioidergic neurotransmission. METHODS: Male Sprague-Dawley rats weighing 150-200g were forced to suffer immobilization stress for 2 hours on each of 14 successive days. Then we examined the maximum binding capacity and affinity of each opioid subtypes(mu, delta, kappa). RESULTS: Repeated immobilization stress increased the binding of [3H]DPDPE on the delta-subtype opioid receptor in the striatum and hypothalamus. Saturation experiments followed by scatchard analyses of the results showed an increase in the density of delta-subtype opioid receptors, but the affinity of the delta-subtype opioid receptor remained unchanged. Repeated immobilization stress reduced enkephalin activity of striatum and hypothalamus. CONCLUSIONS: From these results, it could be concluded that repeated immobilization stress up-regulated the delta-subtype opioid receptors and reduced the activity of enkephalin, an endogenous ligand for the delta-subtype opioid receptor.

Glial Peripheral Benzodiazepine Receptor Mediates the Relief of Acute Stress-Induced Anxiety in Rats / 신경정신의학

OBJECTIVES: Peripheral benzodiazepine receptor has been suggested to be associated with the relief of anxiety response induced by stresses. This study was designed to observe the anxiolytic activity of peripheral benzodiazepine receptor. METHODS: Male Sprague-Dawley rats, weighing 200-250g were forced to suffer an immobilization stress for 2 hours. The level of anxiety by immobilization was performed by an elevated plus maze and was evaluated by the number of [3H]Ro5-4864 binding sites in the olfactory bulb. RESULTS: Saturation experiments followed by scatchard anlayses of the results showed that the density of peripheral benzodiazepine receptor increased and the affinity of the peripheral benzodiazepine receptor remained unchanged. It was found that there was no significant change in the cerebral cortex. Pretreatment with clonazepam, a central benzodiazepine receptor agonist, before an immobilization stress abolished the anxoius response on the performance of plus maze. In this group, upregulation of peripheral benzodiazepine receptor of olfactory bulb was not observed. Ro5-4864, a peripheral benzodiazepine receptor agonist, elicited an increase of anxiolytic response on the performance of plus maze. Progesterone, a precursor of neuroactive steroid, also increased anxiolytic response on the performance of plus maze. Pretreatment with PK11195, a peripheral benzodiazepine receptor antagonist, abolshed the anxiolytic effect of progesterone. CONCLUSIONS: From these results, it could be concluded that peripheral benzodiazepine receptor is closely associated with the relief of acute stress induced anxiety response via an increase of synthesis of neuroactive steroid.

The Effect of Repeated Stress on the Modulation of Neuroactive Steroids at the GABAA-Benzodiazepine Receptor Complex in Rats / 신경정신의학

OBJECTIVES: Pregnanolone is a potent positive modulator of the gamma-aminobutyric acid(GABA) response that enhances the binding of [3H]flunitrazepam to the GABA A receptor. Recently, it was reported that chronic treatment with pregnanolone uncouples allosteric interactions between steroid and benzodiazepine recognition sites. The present study was designed to assess the effect of repeated stress on the modulation of neuroactive steroids on the GABA A receptor. METHODS: The effect of steroids on the ligands binding to GABA A receptor was investigated using cerebral cortices of unstressed and repeatedly immobilized rats. Male Sprague-Dawley rats, weighing 200-250g were forced to suffer an immobilization stress for 2 hours. RESULTS: Pregnanolone enhanced the binding of [3H]flunitrazepam to GABA A receptor in both of unstressed and repeatedly stressed rats. However, repeatedly stressed rats showed significantly higher values in EC50 and lower values in E max of enhancement binding of [3H]flunitrazepam than those of unstressed rats. CONCLUSIONS: From these findings, it can be concluded that repeated stress reduced the positive modulation of neuroactive steroid on the GABA A-receptor complex.