CLONIDINE POTENTIATES THE EFFECTS OF 5-HT1A, 5-HT1B AND 5-HT2A 2C ANTAGONISTS AND 8-OH-DPAT IN THE MOUSE FORCED SWIMMING TEST/

The present study was undertaken to identify the receptor subtypes inv olved in clonidine's ability to enhance the effects of antidepressant drugs in the mouse forced swimming test. Clonidine (0.06 mg/kg, i.p.) significantly enhanced the antidepressant-like effects of subactive do ses of the 5-HT1A receptor agonist, 8-OH-DPAT (1 mg/kg, i.p.; P<0.01); the 5-HT1A receptor antagonist, NAN 190 (0.5 mg/kg, i.p.; P<0.01); th e 5-HT1A/1B autoreceptor antagonist, (+/-) pindolol (32 mg/kg, i.p.; P <0.01); the 5-HT2A/2C receptor antagonist, ritanserin (4 mg/kg, i.p.; P<0.01). Pretreatment with clonidine failed to increase mobility when administered in combination with the 5-HT1B receptor agonist, RU 24969 (1 mg/kg, i.p.) or the 5-HT2A receptor antagonist, ketanserin (8 mg/k g, i.p.). In conclusion, clonidine-induced anti-immobility effects are more likely mediated by 5-HT1A and 5-HT2C receptors, as well as alpha -2-adrenergic autoreceptors situated on noradrenergic neurones. The re sults of the present study also demonstrate that serotonergic receptor function can influence alpha-2-adrenoreceptor mediated responses in t he mouse forced swimming test. (C) 1998 Elsevier Science B.V./ECNP.