The Behavioral and Pharmacological Actions of NMDA Receptor Antagonism are Conserved in Zebrafish Larvae

Dizocilpine maleate (MK-801) is one of several NMDA receptor antagonists that is widely used to pharmacologically model the symptoms of psychosis and schizophrenia in animals. MK-801 elicits behaviors in adult zebrafish (Danio rerio) that are phenotypically consistent with behaviors observed in humans and rodents exposed to tbhe drug. However, the molecular and cellular processes that mediate the psychotomimetic, cognitive and locomotive behaviors of MK-801 are unclear. We exposed zebrafish larvae to MK-801 to assess their merit as a model organism to elucidate the behavioral effects of NMDA receptor blockade. Zebrafish larvae were acutely immersed in MK-801 to assess the effect on spontaneous swimming. MK-801 caused a time- and dose-dependent increase in larval swim speed, and the peak response (a five-fold increase in swim speed) was evoked by a three h exposure to a 20 uM dose. Zebrafish larvae did not exhibit sensitivity to the locomotor effects of MK-801 until 5 dpf, suggesting a critical role for developmental in sensitivity to the drug. Exposure to the low potency NMDA antagonist, memantine, did not alter the swim speed of zebrafish larvae. Co-immersion in D(1) or D(2) dopamine receptor antagonists did not disrupt the time course or magnitude of the increase in swim speed, suggesting dopaminergic signaling is not required for the locomotor actions of MK-801. Our findings of the behavioral actions of MK-801 in zebrafish larvae are consistent with previous observations in mammals and imply that the physiological, cellular and molecular processes disrupted by MK-801 are conserved in zebrafish larvae. These data suggest that the zebrafish larvae is a valid and useful model to elucidate neurobehavioral aspects of NMDA receptor antagonism and may provide insight to the neurobiology of psychosis and schizophrenia.     

Symptom reduction and termination: client change and therapist identified reasons for saying goodbye

Empirical efforts have focused on predicting whether or not clients prematurely terminate therapy, with nonattendance of last session equated to premature termination. However, this fails to explore the relationship between clients’ distress reduction and reasons for termination. With this study, we aimed to understand how clients’ distress change relates to premature termination and examine clients’ distress change in conjunction with therapists’ perceptions of termination reasons. We collected data from 797 clients who prematurely terminated or attended termination but completed therapy a minimum of three individual sessions provided by 38 therapists. Clients completed an assessment of psychological symptoms before each session. At the end of treatment, therapists identified the reasons they believed termination occurred for all clients in the sample. Results demonstrate that total sessions attended and missed predict premature termination, whereas distress change does not. Additionally, clients who were believed to accomplish goals do show greater change. However, therapists’ indicated that over half of clients did not reach goals at termination and they did not perceive nonattendance at last session to equate to drop out in all cases. Implications are discussed with respect to understanding why clients’ terminate, therapeutic goal conceptualization, and review of goals during termination in time-limited psychotherapy.     

Panic disorder and depression: A psychodynamic exploration of comorbidity

Eight of twenty-one patients presenting for treatment in an open trial of brief psychodynamic psychotherapy for panic disorder also carried the diagnosis of major depression. For the patients who completed the study, depression remitted as well as panic disorder. The authors highlight psychodynamic factors that they hypothesize may contribute to the significant overlap between panic disorder and depression, and describe three videotaped cases to illustrate these points.