Excitation and depression of cortical neurones by 5‐hydroxytryptamine
Authors: Roberts M. H. T. , Straughan D. W. 
Published: December 2014

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 α‐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.