TY - JOUR T1 - Chronic infusion of PCP via osmotic mini-pumps: a new rodent model of cognitive deficit in schizophrenia characterized by impaired attentional set-shifting (ID/ED) performance. AU - Pedersen,Christian Spang, AU - Goetghebeur,Pascal, AU - Dias,Rebecca, Y1 - 2009/09/15/ PY - 2009/07/01/received PY - 2009/09/04/revised PY - 2009/09/08/accepted PY - 2009/9/19/entrez PY - 2009/9/19/pubmed PY - 2010/2/27/medline SP - 66 EP - 9 JF - Journal of neuroscience methods JO - J Neurosci Methods VL - 185 IS - 1 N2 - The identification of animal disease-like models for cognitive symptoms in schizophrenia is of central importance to the successful development of pharmacological therapies for psychosis resulting in a functional outcome in patients. Executive function is one of the most severely affected cognitive domains in schizophrenia that remains inadequately treated by existing therapies. The rat attentional set-shifting (or intra-dimensional-extra-dimensional (ID/ED)) task has been developed to test executive function in rodents and successful translation of pre-clinical data into the clinical setting now depends on the identification of a predictive animal disease-like model. The present study investigates whether a continuous 14-day mini-pump infusion of the non-competitive NMDA receptor antagonist phencyclidine (PCP) leads to a deficit in the ID/ED task, and subsequently evaluates the effect of modafinil in this model. Lister hooded rats were implanted subcutaneously with osmotic mini-pumps containing saline or PCP (15 mg/kg/day) for 14 days followed by a 7-day drug-free recovery phase. Rats were then tested in the ID/ED task following an acute injection of either vehicle or modafinil. PCP-treated animals displayed a selective deficit at the ED shift stage resembling that observed in schizophrenic patients. This deficit was reversed by an acute injection of modafinil. The PCP-induced impairment and its reinstatement by modafinil are quantitatively and qualitatively similar to that described earlier by our group following sub-chronic intraperitoneal PCP administration, indicative that sub-chronic PCP infusion via osmotic mini-pumps may represent an attractive alternative to the systemic administration protocols generally employed to date. SN - 1872-678X UR - https://www.unboundmedicine.com/medline/citation/19761795/Chronic_infusion_of_PCP_via_osmotic_mini_pumps:_a_new_rodent_model_of_cognitive_deficit_in_schizophrenia_characterized_by_impaired_attentional_set_shifting__ID/ED__performance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-0270(09)00505-6 DB - PRIME DP - Unbound Medicine ER -