RSDP selectively impairs GABAB(1a,2) receptors located at
glutamatergic terminals. A, the percentage of mEPSC and mIPSC
frequency inhibition by baclofen (bac, 100 μm) and
adenosine (adeno, 100 μm) under control condition
(ACSF, white bars) and after incubation of acute hippocampal slices
from wild-type (WT) mice with RSDP (40 nm, black
bars) for 6 h. Baclofen was significantly less efficient in reducing the
frequency of mEPSCs recorded from CA1 pyramidal neurons incubated with RSDP
than from neurons incubated with ACSF (ACSF, 71.0 ± 5.4% inhibition,
n = 5; RSDP, 7.6 ± 2.2% inhibition, n = 9;
***, p < 0.001, Kolmogorov-Smirnov; see also
supplemental Table S2). RSDP was without effect on adenosine-mediated mEPSC
frequency inhibition (ACSF, 67.0 ± 5.3% inhibition, n = 5;
RSDP, 76.0 ± 3.0% inhibition, n = 9; supplemental Table S2).
As an additional control, RSDP was also without effect on the baseline mEPSC
frequency or amplitude (for values, see supplemental Table S3). RSDP did not
affect the baclofen- or adenosinemediated inhibition of the mIPSCs frequency
recorded from CA1 pyramidal neurons (for values, see supplemental Table S2).
RSDP did not alter the amplitudes of Kir3 current responses induced by
baclofen and adenosine in CA1 pyramidal neurons (n = 6 per
condition). B, RSDP impairs the baclofen-mediated mEPSC frequency
inhibition in 1b-/- mice (ACSF, 67.0 ± 3.0% inhibition;
RSDP, 6.0 ± 2.0%; n = 4; ***, p <
0.001, Kolmogorov-Smirnov). Incubation with RSDP had no effect on baclofen- or
adenosine-mediated effects on the mIPSC frequency (for values, see
supplemental Table S2) or on Kir3 current amplitudes. Baclofen-induced Kir3
current responses were reduced in the 1b-/- when compared with
wild-type mice, as described
(22). C, baclofen
failed to depress the mEPSCs frequency in 1a-/- mice due to the
lack of GABAB heteroreceptors in these mice
(22). The basal mEPSC
frequency in 1a-/- mice was increased (for values, see supplemental
Table S3), as reported previously
(22). RSDP was without effect
on the baclofen- or adenosine-mediated inhibition of the mIPSC frequency (for
values, see supplemental Table S2) or on Kir3 currents in 1a-/-
mice. All values are means ± S.E.