PMC:3813744 / 40972-43581 JSONTXT

{"project":"2_test","denotations":[{"id":"24204954-7870865-87518409","span":{"begin":1796,"end":1798},"obj":"7870865"},{"id":"24204954-15582114-87518410","span":{"begin":1802,"end":1804},"obj":"15582114"},{"id":"T40427","span":{"begin":1796,"end":1798},"obj":"7870865"},{"id":"T4566","span":{"begin":1802,"end":1804},"obj":"15582114"}],"text":"Concluding Remarks\nTaken together the present results, in conjunction with previous studies, suggest that acute 5-HT2CR antagonism is likely to enhance reversal learning in visuospatial assays by acting on receptors located within the OFC. However there is likely to be more significant involvement of other areas, including the hippocampus, in the effects of such antagonists on reversal learning when animals perform an egocentric spatial task. Constitutive loss of the 5-HT2CR has more substantial effects on performance in the present egocentric spatial task which are likely to involve disturbance of function in additional brain areas, including the hippocampus and dorsal striatum.\nNotably, behavioural perseveration may be produced by underlying cognitive deficits of perseverance and learned non-reward and influenced by other factors such as motor impulsivity. The wide range of tasks used to assess reversal learning is likely to pose very different demands and involve these processes to different extents and hence heterogeneity in results is to be anticipated.\nThe present findings may have relevance to the pathology and treatment of the cognitive deficits of schizophrenia, as the cognitive inflexibility deficits of the disease can be produced by specific deficits in perseverance [21]. Similar perseverative deficits were observed in 5-HT2CR KO mice, suggesting that a constitutive loss of the 5-HT2CR may be relevant for understanding the cognitive inflexibility that is characteristic of schizophrenia. Moreover, SB242084 facilitated the ability to overcome perseverative responding, while causing a concurrent increase in learned non-reward. As schizophrenia has been associated with both increased perseverance [21] and attenuated latent inhibition and learned irrelevance [56], [57], a tentative suggestion would be that the 5-HT2CR might be a pharmacologically relevant target for opposing both impairments.\nIn conclusion, the current results show that the 5-HT2CR modulates perseverative responding in an egocentric reversal learning procedure. The pattern of results indicates that serotonergic modulation of visuospatial and egocentric reversal tasks depends on different underlying neural systems and that constitutive loss of 5-HT2C receptors leads to impaired acquisition of egocentric discriminations. An important challenge for future studies will be to specify the nature of these differences in both the tasks and experimental manipulations. This will have particular relevance preclinical tests used to characterise novel pharmacological treatments of human psychopathology."}