VGLUT3 (vesicular glutamate transporter type 3) contribution to the regulation of serotonergic transmission and anxiety - PubMed (original) (raw)

Raphe 5HT1A autoreceptors are desensitized in _Vglut3_−/− mice. a, Characteristic pacemaker activity of 5-HT neurons was similar between wild-type (+/+) and mutant (−/−) animals (_Vglut3_−/−, 1.98 ± 0.19 spikes/s, n = 14; Vglut3+/+, 1.99 ± 0.13 spikes/s, n = 12). Integrated firing rate histograms show that the inhibitory effect of ipsapirone on the electrical activity of DRN 5-HT neurons is less important in _Vglut3_−/− mice when compared with wild-type animals. b, Concentration–response curves of ipsapirone-induced inhibition of the firing of DRN 5-HT neurons. The dotted lines illustrate the graphical determination of ipsapirone EC50 values (abscissa) in both groups (Vglut3+/+, EC50 = 4.19 ± 0.52 10−8

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, n = 10; _Vglut3_−/−, EC50 = 6.32 ± 0.51 10−8

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, n = 10; two-tailed t test, p = 0.009). The concentration–response curve of ipsapirone-induced inhibition in _Vglut3_−/− mice was significantly different from that in Vglut3+/+ mice (n = 10, two-way ANOVA, F = 8.59, p = 0.0038). c, Autoradiograms of brain sections at the level of the DRN, labeled by [35S]GTP-γ-S (50 p

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) in the absence (basal) or the presence (stimulated) of 10−5

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5-CT. The concentration-response curves show a desensitization of 5HT1A autoreceptors in _Vglut3_−/− mice (black circles) when compared with Vglut3+/+ mice (white circles). [35S]GTP-γ-S labeling was indeed significantly lower in mutant animals (two-way ANOVA, F = 10.23, p = 0.004; Bonferroni, 10−7

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p < 0.005, 10−6

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p < 0.01). OD, optical density. d, The 5HT1A autoreceptor antagonist 8-OH-DPAT induced a loss of body temperature in both genotypes. At the lowest dose (0.06 mg/kg, s.c.) the loss of temperature was not significant in wild-type or mutant mice (n = 7 and n = 8, respectively). At the 0.1 mg/kg dose, the temperature loss in _Vglut3_−/− mice (n = 7, −1.2 ± 0.1°C) was significantly less important than in Vglut3+/+ mice (n = 7, −2.1 ± 0.2°C, Mann–Whitney, p = 0.0045). This hyposensitivity of _Vglut3_−/− mice to 8-OH-DPAT-induced hypothermia was confirmed at the dose of 0.3 mg/kg (_Vglut3_−/−, n = 7, −1.8 ± 0.3°C, Vglut3+/+, n = 8, −3.2 ± 0.4°C, Mann–Whitney, p = 0.0278).