Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: KEY RESULTS: Through 5-HT(1A) activation, F15063 partially alleviated (MED: 0.04 mg kg(-1)) PCP-induced social interaction deficit between two adult rats, without effect by itself, underlining its potential to combat negative symptoms. At doses above 0.16 mg kg(-1), F15063 reduced interaction by itself. F15063 (0.16 mg kg(-1)) selectively re-established PCP-impaired 'cognitive flexibility' in a reversal learning task, suggesting potential against adaptability deficits. F15063 (0.04-0.63 mg kg(-1)) also reversed scopolamine-induced amnesia in a juvenile-adult rat social recognition test, indicative of a pro- cholinergic influence. Activity in this latter test is consistent with its D(4) partial agonism, as it was blocked by the D(4) antagonist L745,870. Finally, F15063 up to 40 mg kg(-1) did not disrupt basal prepulse inhibition of startle reflex in rats, a marker of sensorimotor gating. CONCLUSIONS AND IMPLICATIONS: The balance of D(2)/D(3), D(4) and 5-HT(1A) receptor interactions of F15063 yields a promising profile of activity in models of cognitive deficits and negative symptoms of schizophrenia.
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Authors | R Depoortère, A L Auclair, L Bardin, L Bruins Slot, M S Kleven, F Colpaert, B Vacher, A Newman-Tancredi |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 151
Issue 2
Pg. 266-77
(May 2007)
ISSN: 0007-1188 [Print] England |
PMID | 17375085
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Benzofurans
- Benzylamines
- Cyclopentanes
- Dopamine Agonists
- Dopamine Antagonists
- Dopamine D2 Receptor Antagonists
- N-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yloxy)ethyl)-3-(cyclopent-1-enyl)benzylamine
- Receptors, Dopamine D3
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin Receptor Agonists
- Receptors, Dopamine D4
- Phencyclidine
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Topics |
- Amnesia
(physiopathology, prevention & control)
- Animals
- Antipsychotic Agents
(pharmacology)
- Behavior, Animal
(drug effects)
- Benzofurans
(pharmacology)
- Benzylamines
(pharmacology)
- Cognition Disorders
(chemically induced, physiopathology, prevention & control)
- Cyclopentanes
(pharmacology)
- Dopamine Agonists
(pharmacology)
- Dopamine Antagonists
(pharmacology)
- Dopamine D2 Receptor Antagonists
- Dose-Response Relationship, Drug
- Male
- Models, Animal
- Phencyclidine
- Rats
- Rats, Sprague-Dawley
- Receptors, Dopamine D3
(antagonists & inhibitors)
- Receptors, Dopamine D4
(agonists)
- Reflex
(drug effects)
- Reflex, Startle
(drug effects)
- Serotonin 5-HT1 Receptor Agonists
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin Receptor Agonists
(pharmacology)
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