Effect of chronic treatment with 8-OH-DPAT in the forced swimming test requires the integrity of presynaptic serotonergic mechanisms.

The effect of chronic treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on rats' behaviour in the forced swimming test was studied in animals injected intracerebroventricularly with 150 micrograms 5,7-dihydroxytryptamine (5,7-DHT) or given three oral doses of parachlorophenylalanine (PCPA). A single dose of 0.25 mg/kg 8-OH-DPAT significantly reduced rats' immobility in 5,7-DHT-sham-operated animals 24 h after a 14-day schedule of 0.25 mg/kg 8-OH-DPAT or saline subcutaneously twice daily. The effects of acute 8-OH-DPAT in both chronically 8-OH-DPAT- and saline-treated animals were prevented by 5,7-DHT which caused a marked depletion of brain serotonin (5-HT). Since animals treated with both 8-OH-DPAT and 5,7-DHT were more active in an open field than those receiving the substances separately, the forced swimming behaviour was analyzed in more detail in subsequent experiments. PCPA treatment completely prevented the increase in struggling caused by acute and chronic 8-OH-DPAT, administered as in the previous experiment, but did not modify the reduction of floating caused by 8-OH-DPAT. PCPA and 8-OH-DPAT, alone or in combination, did not modify rats' activity in an open field. Finally, 0.5 and 1.0 micrograms 8-OH-DPAT in the nucleus raphe dorsalis significantly increased struggling and reduced floating to the same extent in animals which had received 0.25 mg/kg 8-OH-DPAT or saline subcutaneously twice daily for 14 days. It thus appears that the antidepressant-like effects of chronic treatment with 8-OH-DPAT in the forced swimming test require the integrity of presynaptic serotonergic mechanisms.