Excitation and depression of cortical neurones by 5-hydroxytryptamine.
1. 5-Hydroxytryptamine (5-HT) and various 5-HT antagonists have been applied micro-electrophoretically from multibarrelled micropipettes into the environment of single neurones in the post-sigmoid and suprasylvian gyri of the cat cerebral cortex.2. In unanaesthetized animals (encéphale isolé) a high proportion of neurones (30%) were excited by 5-HT. This excitation usually had a rapid onset and was seen both in spontaneously active neurones and in otherwise quiescent neurones in which firing was induced by L-glutamate. Some neurones were so sensitive that the uncontrolled diffusion from micropipettes was sufficient to excite them. More cells were excited by 5-HT applied as a cation from solutions of the bimaleate salt than when solutions of the creatinine sulphate salt were used.3. In a high proportion of cells (33%) spontaneous firing or amino acid excitation was depressed by 5-HT.4. A mixed effect was seen in a small proportion (6%) of the cells tested; usually 5-HT caused an excitation initially which was followed by a depression. In other cells, desensitization occurred, and the excitatory effect of 5-HT was diminished or lost.5. When glutamate was used to excite otherwise quiescent cells, there was a significant increase in the number of cells excited by 5-HT and a significant decrease in the number of cells unaffected compared with spontaneously active cells.6. The micro-electrophoretic application of D-lysergic diethylamide (LSD 25), 2-brom LSD (BOL 148), methysergide (UML 491), or 2'- (3-dimethylaminopropylthio)cinnamanilide (SQ 10643) temporarily prevented excitation by 5-HT in half the cells tested. LSD and SQ 10643 were particularly potent in this respect. This antagonism of 5-HT excitation could still be seen when excitation of the cell by L-glutamate or acetylcholine (ACh) was unaffected.7. The depression induced by 5-HT was not prevented by the application of known 5-HT antagonists in the majority of the cells tested (93%). In two cells, however, the depression was reversibly prevented by these antagonists.8. Some cells tested with 5-HT were also tested with ACh or (-)-noradrenaline. The response of a cell to ACh was not significantly related to its response to 5-HT. The degree of correlation between the responses to noradrenaline and 5-HT was large, but not statistically significant with the small number of cells studied.9. The effects of 5-HT on cells in animals anaesthetized with alpha-chloralose did not differ significantly from its effects in unanaesthetized preparations. It is suggested that the use of this anaesthetic may prove a useful alternative to unanaesthetized preparations.10. The systemic injection of small quantities of thiopentone sodium selectively and reversibly reduced the sensitivity of some units to excitation by 5-HT at a time when the response to glutamate was unaffected. On other occasions, the 5-HT excitation was unaffected, though the response to glutamate was reduced.11. These results are discussed in relation to the possible nature of the 5-HT receptors in the cerebral cortex, and the interfering effects of anaesthesia on the response of brain cells to potential transmitter substances.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008784:Methysergide / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013874:Thiopental / Q000494:pharmacology
D002934:Cinnamates; D005971:Glutamates; D012702:Serotonin Antagonists; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D013874:Thiopental; D000109:Acetylcholine; D009638:Norepinephrine; D008784:Methysergide