Fig. 5

KalSR^Drd2-KO mice exhibited an ifenprodil-sensitive decrease in anxiety-like behavior in the elevated zero maze. a Male and female control (KalSR^CKO) and KalSR^DAT-KO mice were tested in the elevated zero maze; open area time did not differ between controls and KalSR^DAT-KO mice (with no differences between male and females, data were grouped; N = 49 KalSR^CKO; N = 54 KalSR^DAT-KO). b Male and female control (KalSR^CKO) and KalSR^Drd1a-KO mice were tested in the elevated zero maze; open area time did not differ between controls and KalSR^Drd1a-KO (with no sex differences, data were grouped; N = 7 KalSR^CKO control; N = 12 KalSR^Drd1a-KO). c Both male and female Kal7^Drd2-KO mice exhibited significantly reduced anxiety-like behavior (p < 0.005) compared to control mice (Kal7^CKO) (N = 29 Kal7^CKO, N = 20 Kal7^Drd2-KO males; N = 18 Kal7^CKO, N = 11 Kal7^Drd2-KO females). d Control (Kal7^CKO) and Kal7^Drd2-KO mice were given a 2 mg/kg injection (i.p.) of ifenprodil 10 min before testing for 5 min in the elevated zero maze. Since there was no sex difference (c), data for males and females were pooled. Ifenprodil pretreatment abrogated the genotypic difference (N = 11 each, Kal7^CKO and Kal7^Drd2-KO; pooled data from (a) were repeated for comparison). e Model of dendritic spines in Drd2-expressing neurons of WT and Kal7^KO mice and elevated zero maze response (EZM) before and after blockade of GluN2B-containing GluN receptors by low dose ifenprodil. Model incorporates the decrease in GluN2B seen after Kal7 knockout [9] and the direct interaction of the PH domain of Kal7 with the cytoplasmic tail of GluN2B [28]