Effects of the novel 5-HT(6) receptor antagonist RO4368554 in rat models for cognition and sensorimotor gating
| Autor: | James R. Martin, Marcus J. Zuzow, Krystine Szczepanski, R. Schreiber, Ayhan Şık, Jef Vivian, Jean-Luc Moreau, Susanne van Laarhoven, Arjan Blokland, Rob L. Secchi, Linda Hedley |
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| Přispěvatelé: | Psychiatrie en Neuropsychologie, Neuropsychology & Psychopharmacology, RS: FPN NPPP II |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Reflex Startle Indoles Scopolamine Morris water navigation task Hippocampus Water maze Striatum Nucleus accumbens Neuropsychological Tests Piperazines Rats Sprague-Dawley Cognition medicine Reaction Time Animals Pharmacology (medical) Drug Interactions Rats Wistar Amphetamine Maze Learning Social Behavior Biological Psychiatry 5-HT receptor Gait Disorders Neurologic Pharmacology Analysis of Variance Dose-Response Relationship Drug Rats Dizocilpine Psychiatry and Mental health Disease Models Animal Inhibition Psychological Neurology Acoustic Stimulation Neurology (clinical) Serotonin Antagonists Psychology Neuroscience medicine.drug |
| Zdroj: | European Neuropsychopharmacology, 17 (4), 277-288. Elsevier |
| ISSN: | 0924-977X |
| Popis: | Serotonin(6) (5-HT(6)) receptors are almost exclusively located in the central nervous system. High expression in the hippocampus, nucleus accumbens and striatum is consistent with a potential role in cognition and psychosis. The availability of potent, selective and brain-penetrating 5-HT(6) antagonists such as RO4368554 allows further characterization of the role of the 5-HT(6) receptor in these processes. Herein, we tested RO4368554 in several cognition tasks, as well as sensorimotor gating tests. Using scopolamine-impaired and unimpaired adult male rats, RO4368554 was given in novel object discrimination, social recognition, social discrimination, Morris water maze, passive avoidance and autoshaping procedures. RO4368554 reversed the effects of scopolamine in novel object discrimination (active doses in mg/kg, i.p., 3, 10), social recognition (3, 10), social discrimination (1, 3, 10) and passive avoidance (10, 30 i.p. and 100 p.o.) tasks. In unimpaired rats, RO4368554 enhanced object discrimination (3, 10; 4-h forgetting interval) and autoshaping learning (3), but was inactive in a water maze task (doses tested: 1-10 mg/kg, i.p.). In tests sensitive to antipsychotics, RO4368554 did not reverse sensorimotor gating deficits induced by the psychostimulants dizocilpine and amphetamine (doses tested: 1-30 mg/kg, i.p.) or neonatal lesion of the ventral hippocampus (1-10 mg/kg, i.p.). In conclusion, RO4368554 enhanced learning and memory processes in unimpaired and scopolamine-impaired rats, supporting the notion that the cognitive enhancing effects of 5-HT(6) receptor antagonists involve modulation of cholinergic neurotransmission. |
| Databáze: | OpenAIRE |
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