ABSTRACT
Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-week-old rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-HT2 receptors, but not by the activation of either 5-HT1A or 5-HT3 receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.
Subject(s)
Adult , Animals , Humans , Rats , Aging , Brain , Citalopram , Critical Period, Psychological , Depression , Dominance, Ocular , Fluoxetine , Long-Term Potentiation , N-Methylaspartate , p-Chloroamphetamine , Plastics , Receptors, Serotonin, 5-HT3 , Serotonin , Visual CortexABSTRACT
Hepatocytes were isolated from livers of adult male Sprague-Dawley rats and cultured in Williams'E Medium with [3 H] thymidine. The effect of 5-hydroxytryptamine (5-HT) was investigated through adding various concentrations (10-8～10-3 mol/L) of 5-HT to the hepatocyte cultures in the presence or absence of epidermal growth factor (EGF) and insulin. The involvement of 5-HT2 receptor was examined by adding a 5-HT2 receptor antagonist, ketanserin (10-6 mol/L), to some of the cultures containing 5-HT. The increment of DNA synthesis was measured by [3 H] thymidine incorporation. The results showed that 5-HT2 (≥10-6 mol/L) significantly (P＜0.05) increased the amount of DNA synthesis induced by EGF and insulin in the cultured adult rat hepaptocytes. The effect of 5-HT in enhancing DNA synthesis began to appear at a concentration between 10-7 and 10-6 mol/L and reached maximum at concentrations of ≥10-4 mol/L. The enhancement of DNA synthesis by 5-HT was significantly (P＜0.05) antagonized by ketanserin, suggesting that this effect of 5-HT was mediated by 5-HT2 receptor subtype.
ABSTRACT
Risperidone is one of a new class of atypical antipsychotic drug that combines potent dopamine(D2) and serotonin(5-HT2) receptor antagonist properties. In the last few years, there have been several report of risperidone-induced manic symptoms during treatment of schizoaffective disorder or schizophrenia. We report three cases of mania developed in two schizophrenia patients and one amphetamine-induced psychotic disorder which appear to have been precipitated by rispendone. This inducing effect might be attributed to its ability to block postsynaptic 5-HT2 receptors, a property that distinguishes it self from other antipsychotic agents. The blocking of serotonin receptors by risperidone may create a perceived depletion of serotonin similar to that seen in affective disorder and lead to mania. Therefore, we should be cautions in the treatment of psychotic disorder with risperidone.