Figure 1

Genetic deletion of caveolin-1 (Cav-1) sensitizes mice to the behavioral effects of the psychotomimetic phencyclidine (PCP). (a) Cav-1 knockout (KO) mice exhibit increased sensitivity to PCP disruption of sensory motor gaiting. Littermate wild-type (WT) and Cav-1 KO mice were injected with saline, 4 or 6 mg kg⁻¹ PCP and immediately placed into acoustic startle response chambers. In all, 6 mg kg⁻¹ PCP significantly decreased (disrupted) prepulse inhibition (PPI) at all prepulse levels in WT and Cav-1 KO mice. However, a lower dose of 4 mg kg⁻¹ PCP significantly disrupted PPI in only Cav-1 KO but not WT mice (mean±s.e.m., n=8 to 12 littermate pairs; ^*P<0.05 versus WT saline or Cav-1 KO saline at each prepulse level). (b, c) PCP-induced hyperlocomotion is increased in Cav-1 KO mice. Littermate WT and Cav-1 KO mice were placed into open field locomotion chambers and allowed to acclimate; 30 min later mice were injected with PCP and the total distance traveled (cm) was determined. Cav-1 KO mice exhibited a greater sensitivity to 4 mg kg⁻¹ PCP than WT mice (panel b, mean±s.e.m., n=9 littermate pairs; ^*P<0.05 versus WT mice at time indicated). Cav-1 KO mice also displayed increased total distance traveled in response to 4 and 6 mg kg⁻¹ PCP compared with WT mice (panel c, mean±s.e.m., n=8 to 12 littermate pairs; ^*P<0.05 versus WT mice in each group). (d, e) Stereotypy movement is increased in Cav-1 KO mice in response to 4 mg kg⁻¹ PCP (panel d, mean±s.e.m., n=9 littermate pairs). Cav-1 KO mice displayed increased total stereotypy counts in response to 4 and 6 mg kg⁻¹ PCP compared with WT mice (panel e, mean±s.e.m., n=8 to 12 littermate pairs; ^*P<0.05 versus WT mice in each group).