Experimentally induced supersensitivity of neocortical neurons to microiontophoretically administered serotonin.
Central serotonergic fiber systems of the rat were selectively lesioned by intraventricular injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At various times thereafter, the sensitivity of rostral cortical neurons to microiontophoretically administered serotonin (5-HT) was compared in groups of lesioned and sham-operated animals pretreated with the 5-HT uptake inhibitor CGP 6085. Twenty-four hours after the injection of 5,7-DHT, at which time the cortical 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were both reduced by 40%, there was no significant difference in the sensitivity of cortical neurons to 5-HT. However, 3 days after such treatment, when the cortical 5-HT and 5-HIAA levels were reduced by 52% and 53% respectively, pronounced supersensitivity to 5-HT was noted. The depressant action of 5-HT on neuronal firing was potentiated with regard to both maximal firing depression and duration of the firing inhibition. A similar potentiation of the 5-HT responses was observed 7 days after lesioning. Supersensitivity thus appears to develop between 1 and 3 days after the injection of 5,7-DHT. Seven days after lesioning, the sensitivity of rostral cortical neurons to gamma-aminobutyric acid was unchanged compared to that observed in sham-operated animals.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007478:Iontophoresis; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009627:Nomifensine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D009627:Nomifensine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003891:Desipramine