Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins

Abstract

The injection of 1 microgram of pertussis toxin, which inactivates Gi/o proteins, in the rat dorsal raphe nearly abolished the responsiveness of serotonin (5-HT) neurons to microiontophoretic applications of 5-HT and selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) without altering their responsiveness to of gamma-aminobutyric acid (GABA). In contrast, the injection of 1 microgram of cholera toxin, which causes an activation of Gs proteins, did not alter the responsiveness of 5-HT neurons to 5-HT, 8-OH-DPAT or GABA. Such in situ injection of either toxin in the dorsal hippocampus decreased by about 90% the responsiveness of CA3 pyramidal neurons to microiontophoretic applications onto their cell body of 5-HT and 8-OH-DPAT, but not of GABA. The effectiveness of the stimulation of the ascending 5-HT pathway in suppressing the firing activity of the same neurons, which results from the release of 5-HT at the level of their dendritic tree, was also markedly decreased in the cholera toxin-treated rats, but intriguingly not in the pertussis toxin-treated rats. These results indicate that, on 5-HT neurons, the somato-dendritic 5-HT1A autoreceptor is coupled to Gi/o, but insensitive to the persistent activation of Gs proteins. In the CA3 region of the hippocampus, there would be two subsets of postsynaptic 5-HT1A receptors on the pyramidal neurons: those apposed to 5-HT terminals on their dendritic tree (denoted intrasynaptic) and those located on their cell body (denoted extrasynaptic). The former are cholera toxin sensitive, whereas the latter are sensitive to both pertussis and cholera toxins.