Fig. 5: Treatment with norBNI normalizes sex-specific behavioral phenotypes of male and female DAT Val559 mice. | Molecular Psychiatry

Fig. 5: Treatment with norBNI normalizes sex-specific behavioral phenotypes of male and female DAT Val559 mice.

From: Kappa opioid receptor antagonism restores phosphorylation, trafficking and behavior induced by a disease-associated dopamine transporter variant

Fig. 5

A–D Male-specific phenotype: Male homozygous DAT Val559 mice and their WT littermates were injected with saline (vehicle; n = 13 for WT and 12 for DAT Val559, respectively) or norBNI (10 mg/kg, i.p.; n = 13 for WT and 12 for DAT Val559, respectively) 30 min prior to testing, placed into the center of the open Y-maze and the number of alternating arm entries, distance travelled and direct revisits were recorded as described in Methods. A Representative heat maps showing the explorative behavior of WT and DAT Val559 mice following vehicle or norBNI administration. Time spent in each area is directly correlated to the color gradient ranging from dark blue to dark red, with the latter indicating highest value. B Systemic administration of norBNI 30 min prior to the test normalized the deficit in the percentage of alternations of DAT Val559 mice when compared to WT control mice. C No acute effect of norBNI was observed for total distance travelled during the test session. D Administration of norBNI reduced the number of direct revisits of DAT Val559 mice. E–J Female-specific phenotype: The NOR task was performed with saline treated female WT (n = 11) and DAT Val559 littermates (n = 10) and compared to norBNI treated (10 mg/kg, i.p., 30 min prior to testing) female WT (n = 13) and littermate DAT Val559 (n = 10) mice. E provides representative heat maps representing location in relation to objects (circles) used in NOR sessions. The relative interaction time with the familiar versus the novel object and the discrimination index are shown in (F) and (G), respectively. H shows the total distance travelled and the total object interaction times on day 1 (two novel objects) and day 2 (one novel and one familiar object) are shown in panels (I) and (J), respectively. Data are given as mean and SD and were analyzed using two-way ANOVA with Šídák’s multiple comparisons test. *=P < 0.05, **=P < 0.01, ***=P < 0.001, ****=P < 0.0001, n.s.= not significant.

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