Effects of agonists and antagonists of some serotonin-receptor subtypes on memory and their modulation by the 5-HT-uptake inhibitor fluoxetine.

The memory effects of agonists and antagonists of some serotonin (5-HT)-receptor subtypes were studied in experiments on rats using the method for passive avoidance with punishment reinforcement (step-down). The 5-HT1A-receptor agonist buspirone (1 mg/kg i.p.) elicited behavioural responses which suggested the lack of pronounced effect on learning and retention; the 5-HT1A-receptor antagonists NAN-190 (1 mg/kg i.p.) and pindolol (6 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls. The 5-HT2-receptor antagonist ritanserin (1 mg/kg i.p.) impaired retention tested 24 hours and 7 days after training as compared to controls, while the 5-HT3-receptor antagonist ondansetron (0.1 mg/kg i.p.) improved it. The 5-HT1/5-HT2-receptor antagonist dotarizine (50 mg/kg orally), characterized by a calcium-antagonistic action, too, exerted some facilitating effect on learning. Most of the effects of the 5-HT-receptor agonists and antagonists were changed when the 5-HT concentration in the synaptic region was increased by the 5-HT-uptake inhibitor fluoxetine (20 mg/kg orally). The results suggest different participation of 5-HT1A-, 5-HT2- and 5-HT3-receptors in the mechanisms of memory process and its modulation by the serotonin level in the cerebral serotonergic synapses.