| Schizophrenia is a disease of brain functioning involving severe and pervasive dysfunctions in perception, behavior and cognition. This disease is characterized by positive symptoms (hallucinations, delusions, and bizarre behavior), negative symptoms (flat affect, alogia, anhedonia, and avolition), affective symptoms (suicide and depression), and cognitive deficits (distractibility, loosening of associations, and disorganized behavior). Traditionally, treatment for schizophrenia focused on the elimination of positive symptoms; however, a number of recent studies have established the need for these symptom clusters to be viewed as independent features of the disease that should be individually targeted for treatment. In particular, a relationship between cognitive dysfunction and functional outcome, defined as the ability to function in everyday life, has been demonstrated. Cognitive deficits in schizophrenia have been found to be related to functional outcome measures such as social competence, social problem solving, and psychosocial skill acquisition (Green et al. 2000, Liddle 2000, Braver et al., 1999, Meltzer and McGurk 1999, McGurk and Meltzer 2000) and to be one of the main factors limiting the success of psychosocial treatments aimed at developing or enhancing these skills. Thus, cognitive dysfunction can be considered an obstacle to good treatment outcome (Keefe et al., 1999, Meltzer & McGurk 2000). The purpose of the following studies is to develop a model of cognitive deficits in rats that may be associated with specific cognitive deficits in schizophrenia. Reversal, extinction, and working memory tasks will be evaluated using the Morris water maze. Differences between ketamine and vehicle treated rats were not found in reversal, extinction, and working memory tasks. However, group differences were revealed in ketamine challenge studies. The findings from the present study indicate that the tasks evaluated in the water maze lacked sensitivity to the effects of repeated ketamine administration. A number of preclinical studies have revealed negative findings in cognitive tasks after repeated administration of non-competitive NMDA receptor antagonists which strongly suggests that the value of this preclinical model as a means to develop pharmacological treatments for cognitive dysfunction in schizophrenia should be questioned. |
