Abstract |
Social behaviour is frequently impaired in schizophrenic patients, and current antipsychotics appear poorly effective in alleviating this deficit. SSR181507 is a selective dopamine D2 receptor antagonist and 5-HT1A receptor agonist [Neuropsychopharmacology 28 (2003) 2064] with an atypical antipsychotic profile and additional antidepressant/ anxiolytic activities [Neuropsychopharmacology 28 (2003) 1889]. Here, we sought to assess the efficacy of SSR181507, and of reference antipsychotics and antidepressant/ anxiolytics, to counteract phencyclidine (PCP)-induced social interaction deficit in rats. Pairs of unfamiliar rats were placed for 10 min each day into a dimly lit arena, during four consecutive days. On the test day (5th day), each pair was placed into the arena 30 min after i.p. treatment with PCP (or vehicle) and a challenge compound or vehicle (same for both rats, i.p. or s.c.). The time spent in social interaction was scored during 10 min. PCP (1 mg/kg) decreased social interaction time by about 35%. This effect was fully antagonized by pre-treatment with SSR181507 (1 mg/kg). In contrast, neither haloperidol (0.05 and 0.1 mg/kg) nor clozapine (0.3 and 1 mg/kg) antagonized this PCP-induced deficit. The selective 5-HT1A receptor agonist 8-OH-DPAT (0.025 and 0.05 mg/kg s.c.), but not the anxiolytic diazepam (0.75 and 1.5 mg/kg), also improved social interaction impairment in PCP-treated rats: this would indicate that the 5-HT1A receptor agonist properties of SSR181507 are responsible for the reversal of PCP-induced social deficit. These data suggest that, in addition to its atypical antipsychotic profile and antidepressant/ anxiolytic activities, SSR181507 has a potential therapeutic activity in another key feature of schizophrenia poorly controlled by current antipsychotics, namely deterioration in social functioning.
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Authors | D Boulay, R Depoortère, C Louis, G Perrault, G Griebel, P Soubrié |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 46
Issue 8
Pg. 1121-9
(Jun 2004)
ISSN: 0028-3908 [Print] England |
PMID | 15111019
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- (3-exo)-8-benzoyl-N-(((2S)7-chloro-2,3-dihydro-1,4-benzodioxin-1-yl)methyl)-8-azabicyclo(3.2.1)octane-3-methanamine monohydrochloride
- Antipsychotic Agents
- Dioxanes
- Dopamine D2 Receptor Antagonists
- Receptors, Dopamine D2
- Serotonin 5-HT1 Receptor Agonists
- Tropanes
- Receptor, Serotonin, 5-HT1A
- Phencyclidine
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Topics |
- Animals
- Antipsychotic Agents
(pharmacology)
- Dioxanes
(pharmacology)
- Dopamine D2 Receptor Antagonists
- Interpersonal Relations
- Male
- Phencyclidine
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Serotonin, 5-HT1A
(physiology)
- Receptors, Dopamine D2
(physiology)
- Serotonin 5-HT1 Receptor Agonists
- Social Behavior
- Tropanes
(pharmacology)
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