title: Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition.
abstract: The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195, chenx8@uw.edu dstorm@uw.edu.
authors.forename: Xuanmao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195, Institute of Neurobiology, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Amit
authors.initials: A
authors.lastname: Saraf
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Zweifel
authors.affiliation: Department of Pharmacology, School of Medicine, University of Washington, Seattle, Washington 98195, chenx8@uw.edu dstorm@uw.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Storm
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis*; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D007266:Inhibition, Psychological; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D065808:Prepulse Inhibition / Q000502:physiology*; D016548:Prosencephalon / Q000201:enzymology*; D011897:Random Allocation
chemical_list: D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1
keywords: ADHD; behavioral inhibition; hyperactivity; impulsivity; sociability; type I adenylyl cyclase