Acid-sensing ion channel-1a in the amygdala, a novel therapeutic target in depression-related behavior - PubMed (original) (raw)

ASIC1a antagonists produce antidepressant-like effects in ASIC1a+/+ but not in ASIC1a−/− mice. A, Psalmopoeus cambridgei venom (5 μl, 9 ng/μl, i.c.v.) containing the ASIC1a antagonist PcTx1 significantly decreased immobility in the FST in ASIC1a+/+ mice [venom (n = 11), vehicle (n = 10)], but not in ASIC1a−/− mice [venom (n = 9), vehicle (n = 9)]. Two-way ANOVA with interaction revealed a significant overall model (p < 0.001, F (3,35) = 12.29), and a significant venom by genotype interaction (p < 0.01, F (1,35) = 10.69). Planned contrast tests found a significant effect of venom in ASIC1a+/+ mice (*p < 0.001, t (35) = 4.74), but not in ASIC1a−/− mice (p = 0.946, t (35) = 0.069). B, Similar to P. cambridgei venom, purified PcTx1 peptide (5 μl, 100 n

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, i.c.v.) reduced immobility in ASIC1a+/+ mice [PcTx1 (n = 10), vehicle (n = 4)], but not in ASIC1a−/− mice [PcTx1 (n = 6), vehicle (n = 5)]. Two-way ANOVA found similarly significant effects of the PcTx1 by genotype interaction. Planned contrast tests revealed a significant effect of PcTx1 peptide in ASIC1a+/+ mice (*p = 0.003, t (21) = 3.33) but not in ASIC1a −/− mice (p = 0.626, t (21) = 0.494). C, The ASIC1a antagonist A-317567 (45 μ

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) reversibly blocked acid-evoked currents in cultured mouse cortical neurons, and (D) A-317567 (5 μl, 1 m

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, i.c.v.) reduced FST immobility in ASIC1a+/+ mice [A-317567 (n = 12), vehicle (n = 16)], but not in ASIC1a−/− mice [A-317567 (n = 8), vehicle (n = 8)]. Two-way ANOVA with interaction revealed a significant overall model (p < 0.001, F (3,40) = 14.69), and a significant drug by genotype interaction (p < 0.05, F (1,40) = 5.07). Planned contrast tests found a significant effect of A-317567 in ASIC1a+/+ mice (*p < 0.01, t (40) = 2.92), but not in ASIC1a−/− mice (p = 0.549, t (40) = –0. 61).