Enhancement of antidepressant-like response by
intranasally-administered GALR2 and Y1R agonists in the forced swimming
test
We performed the forced swimming test (FST) to achieve the functional
outcome related to the findings on the ventral hippocampus after the
intranasal coadministration of GALR2 and Y1R agonists. Rats were
pre-exposed to water for 15 minutes in the FST and twenty-four hours
after the intranasal (i.n.) administration the immobility and swimming
parameters were measured during the 5 min test phase to assess signs of
depression-like behavior.
The dose response curve showed that the GALR2 agonist lacked effects at
68 µg and 132 µg in the FST. Regarding the Y1R agonist, the 68 µg dose
was ineffective while the 132 µg induced a significant decrease in the
immobility time (one-way ANOVA, F4,25 = 3.79 , p<0.05,
Supplementary Figure 1a) compared to the rest of the groups
(Newman-Keuls post-hoc test: p<0,05; Supplementary Figure 1a).
Moreover, an increase in the swimming behavior (one-way ANOVA, F4,25 =
3.57, p<0,05; Supplementary Figure 1b) was observed compared
to the rest of the groups (Newman-Keuls post-hoc test: p<0,05;
Supplementary Figure 1b).
Upon the M1145 and the Y1R i.n. coadministration a significant decrease
in the immobility time (one-way ANOVA, F5,30 = 8.96, p<0.001,
Figure 5a) was observed compared with control animals (Newman-Keuls
post-hoc test: p<0,001; Figure 5b), M1145 (Newman-Keuls
post-hoc test: p<0,001; Figure 5b) and Y1R agonist alone
(Newman-Keuls post-hoc test: p<0,01; Figure 5b). Moreover, an
increase in the swimming behavior (one-way ANOVA, F5,30 = 10.58,
p<0,001; Figure 5b) was observed after the combined treatment
compared to the control animals (Newman-Keuls post-hoc test:
p<0,001; Figure 5b), M1145 (Newman-Keuls post-hoc test:
p<0,001; Figure 5b) and Y1R agonist alone (Newman-Keuls
post-hoc test: p<0,05; Figure 1 b). GALR2 contribution in this
result was confirmed since the addition of the GALR2 antagonist M871
counteracted the synergistic effects on immobility (Newman-Keuls
post-hoc test: p<0,01; Figure 5b) and swimming (Newman-Keuls
post-hoc test: p<0,05; Figure 5b) induced by the
coadministration of M1145 and the Y1R agonist in the FST. Importantly,
we confirmed the BDNF influence in this action since the addition of the
TrkB antagonist ANA-12 blocked the synergistic on immobility
(Newman-Keuls post-hoc test: p<0,01; Figure 5b) and swimming
(Newman-Keuls post-hoc test: p<0,05; Figure 5b) induced by the
coadministration of M1145 and the Y1R agonist in the FST.
The i.n. administration of the Y1R agonist decreased the time of
immobility compared to the control (Newman-Keuls post-hoc test:
p<0,05; Figure 5b) and the M1145 (Newman-Keuls post-hoc test:
p<0,05; Figure 5b) animals; while induced an increase in the
swimming behavior compared to the control (Newman-Keuls post-hoc test:
p<0,05; Figure 5b) and the M1145 (Newman-Keuls post-hoc test:
p<0,05; Figure 5b) groups. However, the administration of the
GalR2 agonist M1145 alone lacked effects on the FST (Figure 5b) compared
with the control group.