Figure 5

(A) PTPRD knockout provides leftward shift in the cocaine dose-response relationship for reward. Cocaine conditioned place preference in PTPRD heterozygous knockout and wild-type mice. Mean difference ± SEM in time spent on the cocaine-paired side (y axis) before and after conditioning with different doses of cocaine for wild-type and heterozygous knockout mice. n = 11–12 mice of each genotype for each dose. Data from male and female mice are combined, since gender displayed no significant main effect, interaction with genotype or interaction with dose (ANCOVA, p = 0.096, 0.672 and 0.072, respectively). Inset: Includes data from homozygous knockout mice, which display possibly confounding disabilities in mnemonic testing. ^***p < 0.001. (B, C) Altered learning in the Morris Water maze task in homozygous, although not heterozygous, PTPRD knockouts. (B) Mean ± SEM of the latencies to reach Morris water maze platform for wild-type, heterozygous and homozygous PTPRD knockout mice (repeated-measures ANCOVA genotype × day, p = 0.005). Heterozygous knockout mice displayed no significant deficit in task acquisition (Scheffé post hoc test, p = 0.694), whereas homozygous mice displayed deficits as previously reported (25) (Scheffé post hoc test, p < 0.001). (C) Results of the probe trial confirmed learning deficits of the PTPRD knockout mice (ANCOVA, p = 0.045 for mean distance to platform, p = 0.414 for latency to quadrant, p = 0.006 for time in the target quadrant, and p = 0.003 for swimming speed). The homozygote knockouts were solely responsible for these differences; heterozygote mice did not differ from wild-type animals in any of the measures (Scheffé post hoc test, p = 0.996 for mean distance to platform, p = 0.476 for time in the target quadrant, and p = 0.830 for swimming speed). Data presented are mean ± SEM, n = 8–12/genotype, 1–2 females/group. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001. AT, Change in time spent on drug-paired side; Dist., distance; Qad., quadrant.