title: Inhibiting cyclin-dependent kinase 5 in the nucleus accumbens enhances the expression of amphetamine-induced locomotor conditioning.
abstract: When psychostimulant drugs like amphetamine are administered repeatedly in the presence of a contextual stimulus complex, long-lasting associations form between the unconditioned effects of the drug and the contextual stimuli. Here we assessed the role played by the proline-directed serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) in the nucleus accumbens (NAcc) on the expression of the conditioned locomotion normally observed when rats are returned to a context previously paired with amphetamine. Infusing the Cdk5 inhibitor roscovitine (40nmol/0.5μl/side) into the NAcc 30-min before the test for conditioning significantly enhanced the conditioned locomotor response observed in rats previously administered amphetamine in the test environment. This effect was specific to the expression of a conditioned response as inhibiting Cdk5 produced no effect in control rats previously administered saline or previously administered amphetamine elsewhere. As inhibiting Cdk5 during exposure to amphetamine has been found to block the accrual of locomotor conditioning, the present results suggest distinct roles for NAcc Cdk5 in the induction and expression of excitatory conditioning by amphetamine.
authors.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Singer
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Forneris
authors.affiliation: Committee on Neurobiology, The University of Chicago, Chicago, IL, USA; Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA. Electronic address: pvezina@yoda.bsd.uchicago.edu.
authors.forename: P
authors.initials: P
authors.lastname: Vezina
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077546:Roscovitine; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D011687:Purines; D000077546:Roscovitine; D000661:Amphetamine; D051360:Cyclin-Dependent Kinase 5
keywords: Cdk5; Conditioning; Learning; Locomotion; Psychostimulants; Roscovitine