PMID- 24939858
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 85
DP  - 2014 Oct
TI  - Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 
      signaling in the nucleus accumbens.
PG  - 243-52
LID - S0028-3908(14)00200-7 [pii]
LID - 10.1016/j.neuropharm.2014.05.033 [doi]
AB  - Intermittent systemic exposure to psychostimulants leads to several forms of 
      long-lasting behavioral plasticity including nonassociative sensitization and 
      associative conditioning. In the nucleus accumbens (NAcc), the protein 
      serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation 
      target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute 
      to the neuroadaptations underlying the formation of conditioned associations. 
      Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in 
      dendritic spine density normally observed in this site following repeated 
      cocaine. Mice lacking the Kal7 gene display similar effects. As increases in 
      spine density may relate to the formation of associative memories and both Cdk5 
      and Kal7 regulate the generation of spines following repeated drug exposure, we 
      hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of 
      Kal7 in the NAcc may prevent the induction of drug conditioning. In the present 
      experiments, blockade in rats of NAcc Cdk5 activity with roscovitine 
      (40 nmol/0.5 mul/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; 
      i.p.) prevented the accrual of contextual locomotor conditioning but spared the 
      induction of locomotor sensitization as revealed on tests conducted one week 
      later. Similarly, transient viral expression in the NAcc exclusively during 
      amphetamine exposure of a threonine-alanine mutant form of Kal7 [mKal7(T1590A)] 
      that is not phosphorylated by Cdk5 also prevented the accrual of contextual 
      conditioning and spared the induction of sensitization. These results indicate 
      that signaling via Cdk5 and Kal7 in the NAcc is necessary for the formation of 
      context-drug associations, potentially through the modulation of dendritic spine 
      dynamics in this site.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Singer, Bryan F
AU  - Singer BF
AD  - Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.
FAU - Neugebauer, Nichole M
AU  - Neugebauer NM
AD  - Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 
      Chicago, IL, USA.
FAU - Forneris, Justin
AU  - Forneris J
AD  - Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 
      Chicago, IL, USA.
FAU - Rodvelt, Kelli R
AU  - Rodvelt KR
AD  - Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 
      Chicago, IL, USA.
FAU - Li, Dongdong
AU  - Li D
AD  - Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 
      Chicago, IL, USA.
FAU - Bubula, Nancy
AU  - Bubula N
AD  - Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, 
      Chicago, IL, USA.
FAU - Vezina, Paul
AU  - Vezina P
AD  - 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.
LA  - eng
GR  - UL1 TR000430/TR/NCATS NIH HHS/United States
GR  - F31 DA030021/DA/NIDA NIH HHS/United States
GR  - T32 DA07255/DA/NIDA NIH HHS/United States
GR  - T32 DA007255/DA/NIDA NIH HHS/United States
GR  - R01 DA09397/DA/NIDA NIH HHS/United States
GR  - R01 DA009397/DA/NIDA NIH HHS/United States
GR  - F31 DA030021-01A1/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140602
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Kalrn protein, rat)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Purines)
RN  - 0ES1C2KQ94 (Roscovitine)
RN  - CK833KGX7E (Amphetamine)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, rat)
SB  - IM
MH  - Amphetamine/*pharmacology
MH  - Animals
MH  - Central Nervous System Stimulants/*pharmacology
MH  - Conditioning, Psychological/*drug effects/physiology
MH  - Cyclin-Dependent Kinase 5/antagonists & inhibitors/*metabolism
MH  - Guanine Nucleotide Exchange Factors/genetics/metabolism
MH  - Male
MH  - Motor Activity/*drug effects/physiology
MH  - Mutation
MH  - Nucleus Accumbens/*drug effects/physiology
MH  - Phosphorylation/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Purines/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Roscovitine
MH  - Signal Transduction/drug effects
PMC - PMC4107072
MID - NIHMS602425
OTO - NOTNLM
OT  - Conditioning
OT  - Dendritic spines
OT  - Learning
OT  - Memory
OT  - Psychostimulants
OT  - Roscovitine
OT  - Sensitization
EDAT- 2014/06/19 06:00
MHDA- 2015/03/31 06:00
PMCR- 2015/10/01
CRDT- 2014/06/19 06:00
PHST- 2014/03/01 00:00 [received]
PHST- 2014/05/16 00:00 [revised]
PHST- 2014/05/18 00:00 [accepted]
PHST- 2014/06/19 06:00 [entrez]
PHST- 2014/06/19 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - S0028-3908(14)00200-7 [pii]
AID - 10.1016/j.neuropharm.2014.05.033 [doi]
PST - ppublish
SO  - Neuropharmacology. 2014 Oct;85:243-52. doi: 10.1016/j.neuropharm.2014.05.033. 
      Epub 2014 Jun 2.