Excitation and depression of cortical neurones by 5‐hydroxytryptamine

Abstract

SUMMARY1. 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 (encephale isole) 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. 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 oc-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.

Further Studies on the Mode of Action of Psychotomimetic Drugs: Antagonism of the Excitatory Actions of 5‐hydroxytryptamine by Methylated Derivatives of Tryptamine

“…Only the excitatory effects of 5-HT were found to be antagonized by LSD. Antagonism of 5-HT excitation by LSD has been observed in the cortex (I) a.U ( Roberts & Straughan, 1967), the reticular formation of the pons and medulla (Boakes et al, 1970), and the pontine raphe nuclei (Couch, 1970). There is evidence for a serotoninergic excitatory synaptic input to the pontine raphe, and LSD blocks both synaptic excitation and the excitations produced by microiontophoretically applied 5-HT (Couch, 1970;Bloom, Hoffer, Siggins, Barker & Nicoll, 1972).…”

The Action of Micro‐electrophoretically Applied 1‐3,4‐dihydroxyphenylalanine (Dopa) on Single Cortical Neurones

“…Two barrels of each micropipette contained 4 M NaCl, one barrel for recording action potentials, the other for use in current balancing (Roberts & Straughan, 1967). The remaining barrels contained drug solutions.…”

Amino‐acid induced depression of cortical neurones

“…Details of the techniques used for the extracellular iontophoresis of drugs onto spontaneously firing neurones in the cat posterior sigmoid gyrus have been presented elsewhere (Roberts & Straughan, 1967;Johnson, Roberts & Straughan, 1969b). Anaesthesia was induced by N20-halothane and was maintained either on 75% nitrous oxide in oxygen and 10% halothane, or on intravenous pentobarbitone sodium (25 mg initially, supplemented as necessary).…”