NICOTINE IMPROVES WORKING MEMORY SPAN CAPACITY IN RATS FOLLOWING SUB-CHRONIC KETAMINE EXPOSURE

Samantha L Rushforth (1) , Thomas Steckler (1) , Mohammed Shoaib (1)

1 Institute of Neuroscience

Ketamine, an NMDA receptor antagonist produces cognitive deficits in humans in a battery of tasks involving attention and memory. Nicotine can enhance various indices of cognitive performance including working memory span capacity measured using the odour span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia and to evaluate nicotine, antipsychotic clozapine and the novel mGlu2/3 agonist LY404039 in restoring OST performance. Male hooded Lister rats were trained in the OST, a working memory task involving detection of a novel odour from an increasing number of presented odours until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 & 30mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, graded doses of nicotine (0.025-0.1mg/kg) administered acutely restored performance in ketamine-treated animals while significant improvements in odour span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1-10mg/kg) and LY404039 (0.3-10mg/kg) failed to reverse ketamine-induced deficits in doses that were observed to impair performance in the control groups. These data suggest that sub-chronic ketamine exposure in the OST presents a valuable method to examine novel treatments to restore cognitive impairments associated with neuropsychiatric disorders such as schizophrenia. Moreover, it highlights a central role for neuronal nicotinic receptors as viable targets for intervention that may be useful adjuncts to the currently prescribed anti-psychotics.

Mots clés: Cognition; Animal models; Behavioral Science; Nicotine; Schizophrenia; Antipsychotics

Domaines: Pharmacologie

Samantha L Rushforth, Thomas Steckler, Mohammed Shoaib. NICOTINE IMPROVES WORKING MEMORY SPAN CAPACITY IN RATS FOLLOWING SUB-CHRONIC KETAMINE EXPOSURE. Neuropsychopharmacology, 2011, ⟨10.1038/npp.2011.224⟩. ⟨hal-00683160⟩