Abstract | RATIONALE: OBJECTIVES: Based on the receptor pharmacology of asenapine, the current study assessed the efficacy and mechanism of action of asenapine to improve a subchronic phencyclidine (PCP)-induced deficit in visual recognition memory using the novel object recognition (NOR) paradigm in the rat, a paradigm of relevance to cognition in schizophrenia. METHODS: Female-hooded Lister rats received vehicle or PCP (2 mg/kg, i.p.) for 7 days, followed by a 7-day washout. On the test day, rats were given asenapine (0.001-0.1 mg/kg, s.c.) alone or in combination with the D(1) receptor antagonist SCH-23390 (0.05 mg/kg, i.p.) or 5-HT(1A) receptor antagonist WAY100635 (1 mg/kg, i.p.). Time spent exploring two identical objects during a 3-min acquisition trial (followed by a 1-min intertrial interval) and then a familiar and a novel object for another 3 min (retention trial) were recorded onto videotape and scored blind. RESULTS: In the retention trial, vehicle- but not PCP-treated animals explored the novel object significantly more than the familiar object (p < 0.001). Asenapine (0.01-0.075 mg/kg) reversed PCP-induced deficits in NOR (p < 0.01-0.001) in a dose-related manner. This effect was antagonised by SCH-23390 but not by WAY100635. CONCLUSIONS: These results demonstrate a role for D(1) but not 5-HT(1A) receptor mechanisms in mediating the cognitive effects of asenapine in this rodent model.
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Authors | Shikha Snigdha, Nagi Idris, Ben Grayson, Mohammed Shahid, Jo C Neill |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 214
Issue 4
Pg. 843-53
(Apr 2011)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 21088957
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Benzazepines
- Dibenzocycloheptenes
- Heterocyclic Compounds, 4 or More Rings
- Piperazines
- Pyridines
- Receptors, Dopamine D1
- SCH 23390
- Receptor, Serotonin, 5-HT1A
- N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
- Phencyclidine
- asenapine
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Topics |
- Animals
- Antipsychotic Agents
(pharmacology)
- Behavior, Animal
(drug effects)
- Benzazepines
(pharmacology)
- Dibenzocycloheptenes
- Dose-Response Relationship, Drug
- Female
- Heterocyclic Compounds, 4 or More Rings
(pharmacology)
- Pattern Recognition, Visual
(drug effects)
- Phencyclidine
(pharmacology)
- Piperazines
(pharmacology)
- Pyridines
(pharmacology)
- Rats
- Rats, Inbred Strains
- Receptor, Serotonin, 5-HT1A
(metabolism)
- Receptors, Dopamine D1
(antagonists & inhibitors)
- Recognition, Psychology
(drug effects)
- Time Factors
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