THE INDUCTION OF SEROTONIN(3)-LIKE RECEPTOR SUPERSENSITIVITY AND DOPAMINE-RECEPTOR SUBSENSITIVITY IN THE RAT MEDIAL PREFRONTAL CORTEX AFTER THE INTRAVENTRICULAR ADMINISTRATION OF THE NEUROTOXIN 5,7-DIHYDROXYTRYPTAMINE - A MICROIONTOPHORETIC STUDY

This study examines the effect of intraventricular administration of the neurotoxin 5,7-dihydroxytryptamine on serotonin(1A), serotonin(2) and serotonin(3) receptors in the rat medial prefrontal cortex using in vivo extracellular single cell recording and iontophoresis. Iontophoresis of the serotonin(1A), serotonin(1C,2) and serotonin(3) receptor agonists (+/-)-8-hydroxy-(di-n-propyl)aminotetralin, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane and 2-methylserotonin, respectively, produces a current-dependent (5-80 nA) suppression of the basal firing rate of medial prefrontal cortical cells in sham- and 5,7-dihydroxytryptamine-lesioned rats. The suppression produced by 2-methylserotonin and serotonin was significantly greater in 5,7-dihydroxytryptamine-lesioned rats than in control rats. No significant difference in the spontaneous activity of medial prefrontal cortex cells was observed between experimental and control rats after iontophoresis of (+/-)-8-hydroxy-(di-n-propyl)aminotetralin or (+/-)-1(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. There was no significant difference between the groups regarding the response of medial prefrontal cortex cells to the iontophoresis of GABA, whereas the response of medial prefrontal cortex cells to the iontophoresis of dopamine was significantly attenuated in animals pretreated with 5,7-dihydroxytryptamine compared to controls. Our results indicate that 5,7-dihydroxytryptamine-induced denervation selectively enhances the sensitivity of serotonin(3)-like receptors in the medial prefrontal cortex, which could, at least partially, account for the serotonin denervation supersensitivity. Moreover, the finding that the response of medial prefrontal cortical cells to the iontophoresis of dopamine is attenuated in 5,7-dihydroxytrptamine pretreated rats is consistent with the view that the inhibitory action of dopamine in the medial prefrontal cortex is dependent upon serotonin tone.