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

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.

• Authors: K M Campbell, M B Veldman, M J McGrath, F H Burton
• Journal: Neuroreport (Neuroreport) Vol. 11 Issue 10 Pg. 2335-8 (Jul 14 2000) ISSN: 0959-4965 [Print] England
• PMID: 10923696 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Pentylenetetrazole

Topics

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