NDLI: Nicotine Improves Working Memory Span Capacity in Rats Following Sub-Chronic Ketamine Exposure

Content Provider	PubMed Central
Author	Rushforth, Samantha L. Steckler, Thomas Shoaib, Md
Copyright Year	2011
Abstract	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 odor span task (OST). This study examined the effects of a sub-chronic ketamine treatment to model cognitive deficits associated with schizophrenia, and to evaluate the effectiveness of 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 odor from an increasing number of presented odors until they exhibited asymptotic levels of stable performance. Sub-chronic ketamine exposure (10 and 30 mg/kg i.p. for 5 consecutive days) produced a dose-dependent impairment that was stable beyond 14 days following exposure. In one cohort, administration of graded doses of nicotine (0.025–0.1 mg/kg) acutely restored the performance in ketamine-treated animals, while significant improvements in odor span were observed in control subjects. In a second cohort of rats, acute tests with clozapine (1–10 mg/kg) and LY404039 (0.3–10 mg/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.
Related Links	http://dx.doi.org/10.1038/npp.2011.224
Starting Page	2774
File Format	PDF
ISSN	1740634X
e-ISSN	1740634X
Journal	Neuropsychopharmacology
Issue Number	13
Volume Number	36
Language	English
Publisher	Nature Publishing Group
Publisher Date	2011-12-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article

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