Figure 7

The enzymatic activity-independent or activity-dependent effects of catechol-O-methytransferase (Comt) on the responsiveness to GABA_A receptor agonists. (a) Prefrontal cortex (PFC) Comt overexpression in the Lenti-CAG-Comt- or Lenti-CaMKII-Comt-infected control mice enhanced the response to bretazenil, a GABA_A receptor agonist, and SL651498. Methamphetamine (1 mg kg⁻¹) was intraperitoneally injected with bretazenil (10 mg kg⁻¹) or SL651498 (1 mg kg⁻¹). Stereotypy count from 30 to 60 min after methamphetamine administration is shown. Values are the mean±s.e.m. for 6–10 male mice. ^*P=0.017, ^**P=0.031, ^***P=0.011, ^****P=0.022. (b) Tolcapone failed to reverse the enhanced responsiveness to bretazenil in PFC COMT-overexpressing mice, but increased the responsiveness to bretazenil in GFP-expressing control mice. Tolcapone (30 mg kg⁻¹) was intraperitoneally injected to Lenti-CAG-Comt or -GFP-infected control mice 1 h before administration of methamphetamine (1 mg kg⁻¹). Stereotypy count from 30 to 60 min after methamphetamine administration is shown. Values are the mean±s.e.m. for 6–13 male mice. ^*P=0.017, ^**P=0.031, ^***P=0.011, ^****P=0.050, ^#P=0.026. (c) Tolcapone failed to reverse the treatment effect of Comt overexpression on the enhanced responsiveness to bretazenil in Df1/+ mice. Tolcapone (30 mg kg⁻¹) was intraperitoneally injected to Lenti-CAG-Comt or -GFP-infected Df1/+ or control mice 1 h before administration of methamphetamine (1 mg kg⁻¹). Stereotypy count from 30 to 60 min after methamphetamine administration is shown. Values are the mean±s.e.m. for 6–13 male mice. ^*P=0.048, ^**P=0.019.