Figure 5

Tail suspension-triggered dopamine release observed in ACC was deficient in mutant mice. (a) In vivo microdialysis revealed that control mice (11 floxed mice (5 males and 6 females) at 15–20 weeks of age) augmented the dopamine level in ACC by 1.7-fold from the baseline by tail suspension for 6 min (paired t-test between −20–0 min and 0–20 min, t(10)=−7.99, p=1.18E-05), regardless of gender (male mice, t(4)=−9.02, p=0.0008; female mice, t(5)=−5.5, p=0.002). While the mutants (6 mice at 14–18 weeks of age) also showed small dopamine release (paired t-test between –20–0 min and 0–20 min, t(5)=−3.49, p=0.017), robust difference in tail hanging-triggered dopamine release was observed between controls and mutants (repeated measures ANOVA, F(1,45)=2.44, p=0.07, post-hoc planned comparisons, at 0–20 min, F(1,15)=22.1, *p=0.00028; at 20–40 min, F(1,15)=16.1, *p=0.0011; at 40–60 min, F(1,15)=6.32, *p=0.023; at 60–80 min, F(1,15)=6.03, *p=0.026). Before tail suspension, there was no genotypic difference in the baseline dopamine levels in ACC (0.66 nM for controls and 0.75 nM for mutants (t(15)=−0.34, p=0.74). (b) Tail suspension increased 5-HT levels by 1.2-fold from the baseline in ACC both mutants (6 mice at 14–18 weeks of age; paired t-test between –20–0 min and 0–20 min, t(5)=−4.79, p=0.0049) and controls (9 mice (5 males and 4 females) at 15–20 weeks of age; paired t-test between –20–0 min and 0–20 min, t(8)=−4.31, p=0.002). However, there was no genotypic difference in the degree of 5-HT elevation (repeated measures ANOVA, F(1,39)=0.46, p=0.71). Before the tail suspension, there was no genotypic difference in the baseline 5-HT level in ACC (0.63 nM for controls and 0.68 nM for mutants. (t(13)=−0.19, p=0.85). (c) Mutant mice during dialysate sampling showed increased immobility during 6-min tail suspension, compared to the control mice (t(15)=−5.37, *p=0.0002). (d) A robust inverse correlation was observed between ACC dopamine increase and tail suspension-elicited immobility across genotypes (Pearson’s correlation coefficient, r=−0.75, P=0.00053). (e) In vivo microdialysis revealed that both mutants and controls increased ACC dopamine levels during PR schedule of reinforcement (paired t-test between –20–0 min and 20–40 min, control: t(6)=−4.411, *p=0.0045, mutant: t(6)=−2.83, *p=0.029). No difference in the extent of dopamine increase observed between genotypes (repeated measures ANOVA, F(1,36)=0.181, p=0.91). (f) No difference in the extent of ACC dopamine release following tail pinch for 1 min between genotypes in the first 20-min bin (t(11)=−0.34, p=0.74). Data are mean±SEM; n is indicated in parentheses or plot bars.

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