RT Journal Article
SR Electronic
T1 OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5044
OP 5053
DO 10.1523/JNEUROSCI.19-12-05044.1999
VO 19
IS 12
A1 Keith M. Campbell
A1 Luis de Lecea
A1 Diana M. Severynse
A1 Marc G. Caron
A1 Michael J. McGrath
A1 Sheldon B. Sparber
A1 Li-Yan Sun
A1 Frank H. Burton
YR 1999
UL http://www.jneurosci.org/content/19/12/5044.abstract
AB To study the behavioral role of neurons containing the D1 dopamine receptor (D1+), we have used a genetic neurostimulatory approach. We generated transgenic mice that express an intracellular form of cholera toxin (CT), a neuropotentiating enzyme that chronically activates stimulatory G-protein (Gs) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNS-expressed promoters, confers transgene expression that is regionally restricted to different D1+ CNS subsets in different transgenic lines, we observed distinct but related psychomotor disorders in different D1CT-expressing founders. In a D1CT line in which transgene expression was restricted to the following D1+ CNS regions—the piriform cortex layer II, layers II–III of somatosensory cortical areas, and the intercalated nucleus of the amygdala—D1CT mice showed normal CNS and D1+ neural architecture but increased cAMP content in whole extracts of the piriform and somatosensory cortex. These mice also exhibited a constellation of compulsive behavioral abnormalities that strongly resembled human cortical-limbic–induced compulsive disorders such as obsessive–compulsive disorder (OCD). These compulsive behaviors included episodes of perseverance or repetition of any and all normal behaviors, repetitive nonaggressive biting of siblings during grooming, and repetitive leaping. These results suggest that chronic potentiation of cortical and limbic D1+ neurons thought to induce glutamatergic output to the striatum causes behaviors reminiscent of those in human cortical-limbic–induced compulsive disorders.