8-Hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin 1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphe dorsalis

Abstract

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective serotonin 1A (5-HT 1A) receptor agonist, was studied for its anti-immobility activity in the forced swimming test when administered into the raphe nuclei medianus and dorsalis of rats. At concentrations ranging from 0.5 to 5 μg, 8-OH-DPAT siginificantly reduced the immobility of rats when administered into the nucleus raphe dorsalis, but only 5 μg was effective when administered into the nucleus medianus. The activity of rats in an open-field under conditions identical to those used in the forced swimming test was not significantly changed by various concentrations of 8-OH-DPAT administered into the nucleus raphe dorsalis, but was significantly increased by an infusion of 5 μg 8-OH-DPAT into the nucleus raphe medianus. The effect of an infusion of 1 μg 8-OH-DPAT into the nucleus dorsalis was prevented by infusing 2.5 μg (−)-propranolol or 2.5 μg (−)-pindolol into the same area 5 min before 8-OH-DPAT or by treating the animals with sulpiride systematically (100 mg/kg i.p.) or centrally (in the nucleus accumbens; 1 μg/0.5 μl). The results suggest that 8-OH-DPAT reduces the immobility of rats by activating dopamine transmission, probably in the nucleus accumbens, as a consequence of its ability to reduce the activity of 5-HT neurons that originate in the nucleus raphe dorsalis. In view of the similarities between the effects of well-established antidepressants and 8-OH-DPAT in the forced swimming test, it is suggested that 5-HT 1A receptor agonists may constitute a novel class of antidepressant agents.