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Titolo:
OCD-like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+neurons
Autore:
Campbell, KM; de Lecea, L; Severynse, DM; Caron, MG; McGrath, MJ; Sparber, SB; Sun, LY; Burton, FH;
Indirizzi:
Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA Univ Minnesota Minneapolis MN USA 55455 rmacol, Minneapolis, MN 55455 USA Scripps Clin & Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA Scripps Clin & Res Inst La Jolla CA USA 92037 iol, La Jolla, CA 92037 USA Duke0Univ, Med Ctr, Howard Hughes Med Inst, Dept Cell Biol, Durham, NC 2771 Duke Univ Durham NC USA 27710 s Med Inst, Dept Cell Biol, Durham, NC 2771
Titolo Testata:
JOURNAL OF NEUROSCIENCE
fascicolo: 12, volume: 19, anno: 1999,
pagine: 5044 - 5053
SICI:
0270-6474(19990615)19:12<5044:OBCBAN>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
OBSESSIVE-COMPULSIVE DISORDER; CHOLERA-TOXIN TRANSGENE; DOPAMINE-RECEPTOR; RAT-BRAIN; ADENYLATE-CYCLASE; PREFRONTAL CORTEX; CEREBRAL-CORTEX; DOWN-REGULATION; BASAL GANGLIA; MICE;
Keywords:
transgenic mice; cholera toxin; dopamine; D1 receptor; obsessive-compulsive disorder; cAMP; G-proteins; stereotypy; piriform; somatosensory; intercalated nucleus;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Burton, FH Univolis,esota, Dept Pharmacol, 3-249 Millard H,435 Delaware StSE, Minneap Univ Minnesota 3-249 Millard H,435 Delaware St SE Minneapolis MN USA 55455
Citazione:
K.M. Campbell et al., "OCD-like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+neurons", J NEUROSC, 19(12), 1999, pp. 5044-5053

Abstract

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 (G(s)) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNS-expressed promoters, conferstransgene 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 perseveranceor 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 01:47:57