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

Neuroreport. 2000 Jul 14;11(10):2335-8. doi: 10.1097/00001756-200007140-00053.

Abstract

Seizures can be induced by systemic dopamine D1 receptor agonists or by cortical-limbic neurostimulation non-selectively. Seizures are also often associated with tics and compulsions, which likewise involve cortical-limbic hyperactivity. To determine if selective potentiation of cortical-limbic D1 receptor-expressing (D1+) 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 tics and compulsions. This suggests a dopamine-regulated glutamatergic basis for all three states and may explain why they often co-exist in humans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cerebral Cortex / physiology
  • Cerebral Cortex / physiopathology
  • Disease Models, Animal
  • Humans
  • Limbic System / physiology
  • Limbic System / physiopathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Models, Neurological
  • Neurons / physiology*
  • Obsessive-Compulsive Disorder / physiopathology*
  • Pentylenetetrazole
  • Pyramidal Cells / physiology
  • Seizures / chemically induced
  • Seizures / genetics
  • Seizures / physiopathology*
  • Somatosensory Cortex / physiology
  • Somatosensory Cortex / physiopathology
  • Tourette Syndrome / physiopathology*

Substances

  • Pentylenetetrazole