Details

Autor(en) / Beteiligte

• COUSINS, M. S
• SEIDEN, L. S

Titel

The serotonin-1A receptor antagonist WAY-100635 modifies fluoxetine's antidepressant-like profile on the differential reinforcement of low rates 72-s schedule in rats

Ist Teil von

• Psychopharmacologia, 2000-03, Vol.148 (4), p.438-442

Ort / Verlag

Berlin: Springer

Erscheinungsjahr

2000

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• Recent preclinical and clinical data suggest that co-administration of a serotonin-1A (5-HT-1A) receptor antagonist with an antidepressant drug has greater therapeutic efficacy than when the antidepressant drug is administered alone. The purpose of the present experiment was to determine whether pretreatment with the selective 5-HT-1A receptor antagonist N-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide (WAY-100635; 0.003, 0.03, 0.3 mg/kg, s.c.) would alter the effects of the antidepressant fluoxetine (2.5-10 mg/kg, i.p.) on the differential reinforcement of low-rate 72-s (DRL 72-s) schedule. The DRL 72-s schedule is a behavioral screen selective and sensitive to antidepressant drugs. WAY-100635 had no behavioral effects on its own. The lower doses of fluoxetine (2.5 mg/kg and 5 mg/kg) had no effects, but 10 mg/kg increased reinforcement rate without affecting response rate. The increase in reinforcement rate was blocked by pretreatment with 0.03 mg/kg and 0.3 mg/kg WAY-100635, although the combination of fluoxetine and WAY-100635 also significantly reduced response rate. Interestingly, 0.003 mg/kg or 0.03 mg/kg WAY-100635 administered with 5.0 mg/kg fluoxetine increased reinforcement rate, even though this dose of fluoxetine had no effect on performance. These data demonstrate that the behavioral effects of fluoxetine are modified by 5-HT-1A receptor blockade.