PERTUSSIS TOXIN BLOCKS 5-HT1A AND GABA-B RECEPTOR-MEDIATED INHIBITION OF SEROTONERGIC NEURONS
PERTUSSIS TOXIN BLOCKS 5-HT1A AND GABA-B RECEPTOR-MEDIATED INHIBITION OF SEROTONERGIC NEURONS
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DOI:
10.1016/0014-2999(87)90533-4
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发表时间:
1987-11-10
影响因子:
5
通讯作者:
AGHAJANIAN, GK
中科院分区:
文献类型:
--
作者:
INNIS, RB;AGHAJANIAN, GK
To examine the role of guanine nucleotide binding (G) proteins in receptor-mediated inhibition of serotonin (5-HT) neurons, we intracerebrally injected pertussis toxin (0.5-1.0 .mu.g) into rat midbrain in a region immediately rostral to the dorsal raphe nucleus. The baseline firing rate of extracellularly recorded 5-HT neurons was not significantly affected by pertussis toxin treatment. However, in comparison to saline-injected controls, pertussis toxin-injected animals showed markedly blunted sensitivity to agonists that act at 5-HT autoreceptors (ipsapirone, 5-HT and LSD) and to baclofen, a GABAB agonist. This pertussis toxin-induced blunting of sensitivity was demonstrated in vivo (with intravenous and iontophoretic application of drugs) and in vitro in the dorsal raphe brain slice preparation. The sensitivity of iontophoretically applied GABA itself was not significantly decreased with pertussis toxin treatent, consistent with evidence that GABA administered in this manner acts no dorsal raphe cells mainly through GABAA receptors. Our data provide strong evidence for the role of a pertussis toxin substrate(s) (presumably a G protein(s)) in mediating the inhibition induced by the autoreceptor and GABAB receptor on 5-HT neurons in rat dorsal raphe nucleus.