The Effect of Immobilization Stress and Corticosterone on Haloperidol-induced c-fos Expression in Rat Brain / 대한정신약물학회지

OBJECTIVE: Immediate early gene (IEG), c-fos is known to encode a 62 kDa nuclear protein (Fos) which has a critical role in the stimulus response process of many cells. c-fos can be activated in the central nervous system by a variety of physiological and pharmacological treatment. Recently evidences has been reported suggesting that glucocorticoid hormones, which are released from adrenal cortex in response to stress, may regulate IEG expression. We observed whether immobilization stress or corticosterone altered the induction of c-fos by haloperidol in the nucleus accumbens, lateral striatum, and prefrontal cortex. METHODS: Twenty-four healthy Wistar rats of male sex, weighing 300-450 g, were divided into 6 groups according to injection agents [vehicle (1 mg/kg), haloperidol (1 mg/kg), corticosterone (1 mg/kg), immobilization stress, haloperidol (1 mg/kg) and corticosterone (1 mg/kg), haloperidol (1 mg/kg) and immobilization stress] respectively. Fos-immunoreactivity was measured by counting of Fos-positive neurons in the nucleus accumbens, lateral striatum, and prefrontal cortex. RESULTS: (1) The number of Fos-positive neurons in the nucleus accumbens was significantly decreased in the haloperidol plus immobilization stress group and haloperidol plus corticosterone group compared with that in the haloperidol group (p<0.05). (2) The number of Fos-positive nurons in the lateral striatum was significantly decreased in the haloperidol plus corticosterone group compared with that in the haloperidol group, but the number of Fos-positive neurons in the lateral striatum was not significantly different between the haloperidol plus immobilization stress group and the haloperidol group (p<0.05). (3) The number of Fos-positive neurons in the prefrontal cortex was significantly increased in the haloperidol plus immobilization stress group and haloperidol plus corticosterone group compared with that in the haloperidol group (p<0.05). CONCLUSION: These results suggest that regulatory process exerted by corticosterone may alter the antipsychotic effect of haloperidol.

Four Cases of Seizures Induced by Low Doses of Clozapine in Schizophrenic Patients / 신경정신의학

Clozapine is an atypical antipsychotics that has been shown to be effective in treating patients with refractory schizophrenia and those with intolerance to currently available antipsychotics. It also appears to be less likely to cause extrapyramidal symptoms and tardive dyskinesia. But clozapine has been associated with an unusual high incidence of seizures in patients with no previous history of ictal episodes. Seizures occur in approximately 1% of patients treated with antipsychotic drugs. But the prevalence is higher with clozapine. Clozapine-induced seizures are reported to occur in a dose-related manner by progressively lowering the seizure threshold on most all patients as the dose is increased. But seizure does not usually necessitate discontinuation of clozapine treatment. We experienced four cases of seizure induced by low doses of clozapine treatment in schizophrenic patients. Since most of the seizures have occurred soon after increase of a clozapine dose, they may have been related more to rapid increase in blood clozapine levels than to that of dose. It is also possible that dose did not accurately predict blood levels for these patients. The possibility of seizures should not pose a barrier to clozapine treatment for patients with refractory psychotic disorders. The risks and morbidity of seizures can be minimized through attention to clinical management.

Effects of Methysergide on Serum Growth Hormone Response after Electroconvulsive Therapy / 대한정신약물학회지

OBJECTIVES: The purpose of this study was to investigate the effects of methysergide(serotonin receptor antagonist) on serum growth hormone response after electroconvulsive therapy(ECT). METHODS: We studied the changes of the serum growth hormone levels of the day before ECT(No ECT), ECT without methysergide pretreatment(ECT alone), and ECT with methysergide pretreatment(M+ECT) by radioimmunoassay method in 14 psychiatric patients. ECT was induced by the application of 110 volts for a period 0.3-1.0 second, using bitemporal electrodes. RESULTS: 1) Serum growth hormone levels at 15, 30, and 60 minutes after ECT were significantly increased in the ECT alone group than in the No ECT group(p<0.05). 2) Serum growth hormone levels at 15, 30, and 60 minites after ECT were significantly decreased in the M+ECT group than in the ECT alone group(p<0.05). CONCLUSION: These results suggest that the response of growth hormone after ECT seems to be mediated by the activation of serotonergic system.