SynCAM 1 contributes to cocaine sensitization during withdrawal. Mice received daily injections of saline or cocaine (15 mg/kg) over 9–10 days, followed by 15–17 days without injections. On the test day, mice received a saline or cocaine (15 mg/kg) challenge and locomotor activity was measured. (a) WT mice injected for 9–10 days with saline showed elevated locomotor activity in response to the cocaine challenge compared with a saline challenge. In cocaine-withdrawn WT mice, a cocaine challenge further increased locomotor activity as compared with a saline challenge (n=14, 11, 5, 11 mice for cohorts left to right). *P<0.05; ***P<0.001; (b) SynCAM 1 KO mice injected for 9 days with saline showed elevated locomotor activity in response to the cocaine injection compared with a saline injection. Challenging cocaine-withdrawn SynCAM 1 KO mice with cocaine did not further increase locomotor activity as compared with mice that received only a single cocaine injection. Locomotor activities were similar to those observed following a single cocaine injection in the sensitization paradigm (see Figure 3e). Data were obtained from littermates with the experimenter blind to condition. (n=10, 9, 9, 10 mice for cohorts shown left to right) *P<0.05; NS, not significant.