TS+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 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.
Campbell
K M
KM
Department of Pharmacology, University of Minnesota, Minneapolis 55455, USA.
Veldman
M B
MB
McGrath
M J
MJ
Burton
F H
FH
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008032:Limbic System / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D010433:Pentylenetetrazole; D017966:Pyramidal Cells / Q000502:physiology; D012640:Seizures / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D013003:Somatosensory Cortex / Q000502:physiology / Q000503:physiopathology; D005879:Tourette Syndrome / Q000503:physiopathology*
D010433:Pentylenetetrazole