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

Seizures can be induced by systemic dopamine D1 receptor agonists or by cortical-limbic neurostimulation non-selectively. Seizures are also often associated with ties and compulsions, which likewise involve cortical-limbic hyperactivity. To determine if selective potentiation of cortical-limbic D1 receptor-expressing (DIS) neurons increases seizure susceptibility, we administered pentylenetetrazole (PTZ) to mice that express a neuropotentiating transgene only in a glutamatergic, cortical-limbic subset of D1+ neurons (D1CT-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 cortical-limbic D1+ neuropotentiation facilitates not only epilepsy but also ties and compulsions. This suggests a dopamine-regulated glutamatergic basis for all three states and may explain why they often co-exist in humans. NeuroReport 11:2335-2338 (C) 2000 Lippincott Williams & Wilkins.