TS plus OCD-like neuropotentiated mice are supersensitive to seizure induction

Seizures can be induced by systemic dopamine D1 receptor agonists or by cor tical-limbic neurostimulation non-selectively. Seizures are also often asso ciated with ties and compulsions, which likewise involve cortical-limbic hy peractivity. To determine if selective potentiation of cortical-limbic D1 r eceptor-expressing (DIS) neurons increases seizure susceptibility, we admin istered pentylenetetrazole (PTZ) to mice that express a neuropotentiating t ransgene only in a glutamatergic, cortical-limbic subset of D1+ neurons (D1 CT-7 line). These mice exhibited increased PTZ-dependent seizure incidence, onset rate and intensity. Because D1CT-7 mice also exhibit tic+compulsion- like behaviors, this implies that glutamatergic hyperactivity induced by co rtical-limbic D1+ neuropotentiation facilitates not only epilepsy but also ties and compulsions. This suggests a dopamine-regulated glutamatergic basi s for all three states and may explain why they often co-exist in humans. N euroReport 11:2335-2338 (C) 2000 Lippincott Williams & Wilkins.