Idazoxan blocks the nicotine-induced reversal of the memory impairment caused by the NMDA glutamate receptor antagonist dizocilpine.
Journal Article
RATIONALE: Alpha2-adrenoreceptor (alpha(2)-AR) antagonists have been shown to improve, while alpha(2)-AR agonists impair cognitive function in subjects with functioning NMDA receptors (NMDAR). In subjects with inhibited NMDAR (a model of schizophrenia) alpha(2)-AR agonists attenuate the cognitive impairments. The effect with alpha(2)-AR antagonists remains unclear. OBJECTIVES: We investigated the effects of the alpha(2)-AR antagonist idazoxan on memory function in rats treated/not treated with NMDAR antagonist dizocilpine or a combination of dizocilpine and nicotine to clarify noradrenergic/cholinergic regulation of memory function. METHODS: Female Sprague-Dawley rats (n=12) were trained for food reward on the radial maze. Working and reference memory errors and response latency were assessed after injections of idazoxan (0.5, 1.0 mg/kg), dizocilpine (0.05 mg/kg), nicotine (0.2, 0.4 mg/kg) or vehicle, alone or in combination. RESULTS: Dizocilpine potently impaired memory. Nicotine (0.4 mg/kg) reversed this impairment. Idazoxan at the doses tested did not affect performance when given alone or with dizocilpine, but it did block the nicotine reversal of the dizocilpine-induced memory impairment. Three rats after 10-12 drug treatments developed limbic seizures. Our findings suggest that combination of drugs which block alpha(2)-AR with nicotinic agonists in schizophrenia may prevent therapeutic effect of nicotinic agonists and increase risk for convulsive activity with repeated administration.
Full Text
Duke Authors
Cited Authors
- Timofeeva, OA; Levin, ED
Published Date
- September 2008
Published In
Volume / Issue
- 90 / 3
Start / End Page
- 372 - 381
PubMed ID
- 18456310
Pubmed Central ID
- 18456310
International Standard Serial Number (ISSN)
- 0091-3057
Digital Object Identifier (DOI)
- 10.1016/j.pbb.2008.03.011
Language
- eng
Conference Location
- United States