Plasma levels of interleukin-8 and response to paroxetine in patients with major depressive disorder.

OBJECTIVES: Immune dysregulation plays a key role in major depressive disorder (MDD). However, little is known about the complicated involvement of various interleukins in MDD. This study was performed to investigate the correlation between plasma interleukin-8 (IL-8) levels and treatment outcome of paroxetine (a selective serotonin reuptake inhibitor) in patients with MDD. METHODS: A total of 115 hospitalized patients (36 males and 79 females), aged from 18 to 72 years, were enrolled. Plasma levels of IL-8 were measured before treatment initiation (baseline) and at 8 weeks after oral paroxetine treatment. Efficacy of paroxetine was evaluated by use of the Hamilton Depression Rating Scale (HAMD-17). Baseline IL-8 levels were compared between responders and non-responders to paroxetine treatment. RESULTS: Plasma IL-8 levels decreased significantly after an 8-week antidepressant treatment in responders, in association with a dramatic decrease in HAMD-17 scores. In non-responders, plasma IL-8 levels did not change significantly at 8 weeks after antidepressant treatment. Baseline plasma IL-8 levels were found to be significantly lower in responders than in non-responders, showing a correlation between IL-8 and antidepressant response to paroxetine. CONCLUSIONS: These results indicate that plasma IL-8 levels were related to treatment outcome of paroxetine, and therefore suggest that IL-8 could be a promising predicator of treatment response in individual patients with MDD.

[Animal models of schizophrenia using different laboratory mouse strains].

Based on the glutamate dysfunction hypothesis for the pathophysiology of schizophrenia, MK801, a noncompetitive antagonist for the NMDA-type of glutamate receptors, was administered to mice by i.p. injection. We observed hyperlocomotion and stereotypy, two behavioral signs indicative of schizophrenic symptoms in human. Aided with automated movement measuring of locomotion and videotaping for off-line scoring of stereotypy, these two schizophrenia-like behaviors were readily evaluated. According to the result of dose-response measurements of serial MK801 dosages in the BALB/c inbred mice, 0.6 mg/kg MK801 was determined as the optimum dosage for these behaviors. Furthermore, the same experiments were performed in another inbred strain C57BL/6 and the outbred stock ICR, and similar results were obtained. These results show that MK801 induces schizophrenia-like symptoms in both inbred and outbred mice. Risperidone, an atypical antipsychotic drug for treating schizophrenia in human, was used in the schizophrenia models using BALB/c and C57BL/6 mice. The results indicated that risperidone dose-dependently inhibited the MK801-induced schizophrenia-like symptoms in BALB/c and C57BL/6 mice. Thus, our results indicate that the MK801-induced behaviors may serve as useful mouse models of schizophrenia.

Effect of GNTI, a kappa opioid receptor antagonist, on MK-801-induced hyperlocomotion and stereotypy in mice.

AIM: To examine the effect of GNTI [5'-guanidinyl-17-(cyclopropylmethyl)-6,7- dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan], a selective antagonist for the kappa opioid receptor, in the MK-801 (dizocilpine maleate)-induced behavioral model of psychosis in schizophrenia as a way to explore the involvement of the kappa opioid receptor in modulating psychotic symptoms of schizophrenia. METHODS: Two doses of MK-801 (0.3 mg/kg and 0.6 mg/kg) were administered by systemic injection in mice to induce psychosis-like behavior as a rodent schizophrenia model, preceded by an injection of different doses of GNTI. Both locomotion and stereotypy were measured as the behavioral endpoints for quantitative analysis. RESULTS: GNTI inhibited MK-801-induced hyperlocomotion and stereotypy. In particular, GNTI showed differential modulation of stereotypy induced by 0.3 mg/kg vs 0.6 mg/kg MK-801. CONCLUSION: Antagonism of kappa opioid receptors attenuates MK-801-induced behavior, suggesting a potential involvement of the kappa opioid receptor in psychosis-like symptoms of schizophrenia. GNTI appears to be a useful pharmacological tool to explore the kappa opioid receptor function in vivo.