Clozapine and Olanzapine but not Risperidone Impair the Pre-Frontal Striatal System in relation to Egocentric Spatial Orientation in a Y-Maze

Abstract

Many studies indicate a dissociation between two forms of orientation: allocentric orientation, in which an organism orients on the basis of cues external to the organism, and egocentric spatial orientation (ESO) by which an organism orients on the basis of proprioceptive information. While allocentric orientation is mediated primarily by the hippocampus and its afferent and efferent connections, ESO is mediated by the prefronto-striatal system. Striatal lesions as well as classical neuroleptics, which block dopamine receptors, act through the prefronto-striatal system and impair ESO. The purpose of the present study was to determine the effects of the atypical antipsychotics clozapine, olanzapine and risperidone which are believed to exert its antipsychotic effects mainly by dopaminergic, cholinergic and serotonergic mechanisms. A delayed-two-alternative-choice-task, under conditions that required ESO and at the same time excluded allocentric spatial orientation was used. Clozapine and olanzapine treated rats made more errors than risperidone treated rats in the delayed alternation in comparison with the controls. Motor abilities were not impaired by any of the drugs. Thus, with regard to the delayed alternation requiring ESO, clozapine and olanzapine but not risperidone affects the prefronto-striatal system in a similar way as classical neuroleptics does.

Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats

“…In fact, several authors argue that APDs may worsen cognition, particularly typical first generation APDs (Kasper and Resinger, 2003; Woodward et al, 2007). Similar findings have been reported in rodent studies, with either no effect (Kamei et al, 2006), or impaired working and recognition memory following olanzapine and clozapine administration (Addy and Levin, 2002; Castro et al, 2007; Levin and Christopher, 2006; Levin et al, 2005; Ortega-Alvaro et al, 2006). On the contrary, olanzapine, clozapine and ziprasidone attenuate cognitive deficits following phencyclidine and MK-801 treatment in rodents (Abdul-Monim et al, 2006; Karasawa et al, 2008).…”

“…On the other hand, APDs olanzapine and risperidone exacerbated deficits in spatial working memory and attention during the Oculomotor Delayed Response task (Reilly et al, 2007) and decreased dorsolateral prefrontal cortex activation during motor learning tasks (Keedy et al, 2015) in previously APD-naïve schizophrenia patients after 4-6 weeks of treatment. In rodents, olanzapine impaired working memory during Y-Maze and Eight-Arm Radial Maze tests (Castro et al, 2007; Levin et al, 2005; Ortega-Alvaro et al, 2006), and reduced memory acquisition and retrieval in mice during the modified Elevated Plus Maze task (Mutlu et al, 2011). Clinically, APDs can cause varying degrees of sedation (Leucht et al, 2009) and it is possible that sedation impacted the cognitive data.…”

High levels of Cellular Prion Protein improve astrocyte development

“…In addition, PrP C acts as a receptor for the laminin γ‐1 chain and the transmembrane protein neuronal cell adhesion molecule (NCAM), which mediates neuronal adhesion and neurite outgrowth [19,20,22]. In vivo studies showed that interactions of PrP C with laminin γ‐1 chain or the Stress Inducible Protein 1 (STI1), another PrP C ligand, are involved with memory consolidation [23,24].…”