PINDOLOL DOES NOT ACT ONLY ON 5-HT1A RECEPTORS IN AUGMENTING ANTIDEPRESSANT ACTIVITY IN THE MOUSE FORCED SWIMMING TEST

The present study was undertaken to identify the receptor subtypes inv olved in (+/-) pindolol's ability to enhance the effects of antidepres sant drugs in the mouse forced swimming test. Interaction studies were performed with S 15535 (presynaptic 5-HT1A receptor agonist) and meth iothepin (5-HT1B autore ceptor antagonist) in an attempt to attenuate or potentiate antidepressant-like activity. (+/-) Pindolol was tested in combination with selective agonists and antagonists at 5-HT1, 5-HT2 and 5-HT3 receptor subtypes. Pretreatment with S 15535 and methiothep in attenuated the activity of parosetine, fluvoxamine and citalopram ( 32 mg/kg, IP: P < 0.01). (+/-) Pindolol (32 mg/kg, IP.) induced signif icant anti-immobility effects when tested in combination with -methoxy -3(1,2,3,6-tetrahydro-4-pyridyl)-1H-indole (RU 24969) (1 mg/kg, IP; P < 0.05), 1-(2-methoxyphenyl)-4-[-(2-naphthalimido) butyl]piperazine) ( NAN 190) (0.5 mg/kg, P < 0.05) and ondansetron (0.00001 mg/kg, IP; P < 0.01). Pretreatment with NAN 190 (0.5 mg/kg, IP) potentiated the effe cts of RU 24969 (1 mg/kg, IP; P < 0.05) and (+/-) pindolol (32 mg/kg: IP; P < 0.05) the forced swimming test, as did ondansetron (0.00001 mg /kg, IP). Significant additive effects there induced when RU 24969 (1 mg/kg, IP) was tested in combination with NAN 190 (0.5 mg/kg, IP; P < 0.05), (+/-) pindolol (32 mg/kg, IP: P < 0.05) and ondansetron (0.0000 mg/kg, IP; P < 0.05). 8-Hydroxy-3-(di-n-propylamino)tetralin (8-OH-DP AT) (1 mg/kg, IP) or ketanserin (8 mg/kg, IP) did not induce significa nt antidepressant-like effects with any of the agonists/antagonists te sted. The results of the present study suggest that pindolol is acting at presynaptic 5-HT1B serotonergic receptors, in addition to the 5-HT 1A subtype, in augmenting the activity of antidepressants in the mouse forced swimming test.