Responsiveness of cortical neurons to serotonin after 5,7-DHT denervation or PCPA depletion.
1. In adult rats under urethane anesthesia, a vast majority of spontaneously active neurons in the frontoparietal cortex undergo a prolonged depression of their firing rate upon microiontophoretic application of 5-HT. 2. In 5,7-DHT-deafferented cortex, this effect is of a longer duration (mean 14 min) than in controls (mean 5 min). Moreover, small ejection currents of 5-HT are sufficient to induce a prolonged depression of the firing rate. 3. In PCPA-pretreated rats, there are no changes in the responsiveness to 5-HT. 4. In control and PCPA-pretreated rats, blocking of the 5-HT reuptake with fluoxetine increases the duration of responses to 5-HT (mean 15 min), whereas small ejection currents remain without effect. 5. These data indicate that, in the cerebral cortex, denervation supersensitivity to 5-HT results primarily from the removal of 5-HT afferents, and not from depletion of their 5-HT content. The enhanced responsiveness to microiontophoresed 5-HT appears to be due to a suppression of reuptake mechanisms, mainly responsible for the prolongation of 5-HT effects, and to a modification of receptors on target cells, which accounts for their greater sensitivity to 5-HT.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D010134:Fenclonine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology*
D004102:Dihydroxytryptamines; D005473:Fluoxetine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D010134:Fenclonine; D003891:Desipramine