Asenapine improves phencyclidine-induced object recognition deficits in the rat: evidence for engagement of a dopamine D1 receptor mechanism

• Published in: Psychopharmacologia 2011-04, Vol.214 (4), p.843-853
• Main Authors: Snigdha, Shikha, Idris, Nagi, Grayson, Ben, Shahid, Mohammed, Neill, Jo C.
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Antipsychotic Agents - pharmacology; Behavior, Animal - drug effects; Benzazepines - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Dose-Response Relationship, Drug; Female; Heterocyclic Compounds, 4 or More Rings - pharmacology; Medical sciences; Neuropharmacology; Neurosciences; Original Investigation; Pattern Recognition, Visual - drug effects; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phencyclidine - pharmacology; Piperazines - pharmacology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Pyridines - pharmacology; Rats; Rats, Inbred Strains; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Dopamine D1 - antagonists & inhibitors; Recognition (Psychology) - drug effects; Schizophrenia; Time Factors
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-010-2091-5

Rationale Cognitive deficits are common in schizophrenia. Asenapine is an atypical antipsychotic approved by the US Food and Drug Administration in adults for treatment of schizophrenia or acute treatment, as monotherapy or adjunct therapy to lithium or valproate, of manic or mixed episodes of bipolar I disorder. 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.