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Terminal serotonin autoreceptor function in the rat hippocampus is not modified by pertussis and cholera toxins

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Summary

The possibility that the terminal serotonin (5-HT) autoreceptor in the rat hippocampus is coupled to Gi, Go or Gs regulatory proteins was investigated using the electrically evoked overflow of [3H]5-HT from preloaded slices. Pertussis toxin, which inactivates Gi/o or cholera toxin, which stimulates GS, was injected directly in the hippocampus 3 to 11 days prior to the experiments. Hippocampus slices were prepared, loaded with [3H]5-HT, superfused continuously, and stimulated electrically 72 min (S1) and 116 min (S2) after the beginning of superfusion. In the absence of any drug, the evoked overflow of [3H]5-HT in S1 was not altered by either toxin. The enhancing effect of the 5-HT reuptake blocker paroxetine (1 μmol/I) on the evoked [3H]5-HT overflow was also unaltered by these toxins. 5-Carboxyamidotryptamine, a 5-HT autoreceptor agonist, inhibited in a concentration-dependent manner the stimulation-evoked release of [3H]5-HT The concentration-effect curve (0.001–0.1 μmol/I) for this drug was not altered by pretreatment with either pertussis or cholera toxin. Similarly, the effect of another 5-HT autoreceptor agonist, 5-methoxytryptamine (0.1 and I μmol/I), was not altered in the pretreated rats. In addition, the reduction of [3H]5-HT overflow obtained by increasing the stimulation frequency from 1 Hz to 5 Hz, which is due to an increase in terminal 5-HT autoreceptor activation at the higher frequency, was not altered by either toxin. The enhancing effect of the 5-HT autoreceptor antagonist methiothepin (1 μmol/I) on stimulation-evoked [3H]5-HT overflow was not changed by either pretreatment. N-Ethylmaleimide inactivates Gi/o proteins by alkylation. Preincubation with 30 μmol/I N-ethylmaleimide for 30 min did not alter the efficacy of the 5-HT reuptake blocker paroxetine to enhance [3H]5-HT overflow nor did it alter the attenuating effect of 5-methoxytryptamine and the differential effectiveness of 1 and 5 Hz stimulations on the overflow of [3H]5-HT In conclusion, the results suggest that the terminal 5-HT autoreceptor in the rat hippocampus may not be coupled to Gi, Go or Gs proteins.

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Blier, P. Terminal serotonin autoreceptor function in the rat hippocampus is not modified by pertussis and cholera toxins. Naunyn-Schmiedeberg's Arch Pharmacol 344, 160–166 (1991). https://doi.org/10.1007/BF00167213

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