Cyclin-Dependent Kinase Inhibitor 1a (p21) Modulates Response to Cocaine and Motivated Behaviors

The Journal of Pharmacology and Experimental Therapeutics
Natalie E ScholpaBrian S Cummings

Abstract

This study investigated the functional role of cyclin-dependent kinase inhibitor 1a (Cdkn1a or p21) in cocaine-induced responses using a knockout mouse model. Acute locomotor activity after cocaine administration (15 mg/kg, i.p.) was decreased in p21(-/-) mice, whereas cocaine-induced place preference was enhanced. Interestingly, κ-opioid-induced place aversion was also significantly enhanced. Concentration-dependent analysis of locomotor activity in response to cocaine demonstrated a rightward shift in the p21(-/-) mice. Pretreatment with a 5-hydroxytryptamine receptor antagonist did not alter the enhancement of cocaine-induced conditioned place preference in p21(-/-) mice, indicating a lack of involvement of serotonergic signaling in this response. Cocaine exposure increased p21 expression exclusively in the ventral sector of the hippocampus of rodents after either contingent or noncontingent drug administration. Increased p21 expression was accompanied by increased histone acetylation of the p21 promoter region in rats. Finally, increased neurogenesis in the dorsal hippocampus of p21(-/-) mice was also observed. These results show that functional loss of p21 altered the acute locomotor response to cocaine and the conditioned...Continue Reading

References

Nov 1, 1990·Brain Research Bulletin·P G Henke
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·M B MoserR G Morris
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·I SoraG R Uhl
Apr 9, 1999·Nature Neuroscience·E GouldT J Shors
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·X ZhuangR Hen
Apr 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·I SoraG R Uhl
Nov 21, 2002·Hippocampus·Tracey J ShorsElizabeth Gould
Feb 1, 1957·Journal of Neurology, Neurosurgery, and Psychiatry·W B SCOVILLE, B MILNER
Oct 24, 2003·The Journal of Comparative Neurology·Jason P BrownH Georg Kuhn
Nov 16, 2004·Annals of the New York Academy of Sciences·M YamaguchiT Asada
Mar 25, 2005·Physiological Reviews·Djoher Nora AbrousMichel Le Moal
Jun 13, 2006·The Journal of Pharmacology and Experimental Therapeutics·Shuxian HuPhillip K Peterson
Jun 5, 2007·Progress in Neuro-psychopharmacology & Biological Psychiatry·Monica L AndersenSergio Tufik
Nov 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thomas S HnaskoRichard D Palmiter
Mar 28, 2008·The European Journal of Neuroscience·J Martin WojtowiczGordon Winocur
Feb 18, 2009·Genes, Brain, and Behavior·Paul J MeyerTamara J Phillips
Jul 15, 2009·Neurobiology of Learning and Memory·Lakshmi KelamangalathJohn J Wagner
Nov 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jason S SnyderHeather A Cameron
Jan 8, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michele A NoonanAmelia J Eisch
Jan 28, 2010·The European Journal of Neuroscience·M J García-FusterH Akil
Jul 3, 2010·Hormones and Behavior·Quincey LaPlant, Eric J Nestler
Jul 17, 2010·Journal of Neurochemistry·Erin B LarsonDavid W Self
Jan 6, 2011·Addiction·Chloe C Y WongCathy Fernandes
Apr 6, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zhifeng ZhouDavid Goldman
Oct 13, 2011·Nature Reviews. Neuroscience·Alfred J Robison, Eric J Nestler
Jan 27, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jeffrey S SmithCharles Chavkin
Apr 11, 2012·Pharmacology, Biochemistry, and Behavior·Glenn R Valdez, Erin Harshberger
Aug 23, 2012·Pharmacogenomics·David A NielsenThomas R Kosten
Dec 14, 2012·American Journal of Physiology. Renal Physiology·Hang YuanRama Natarajan
Jan 30, 2013·Cold Spring Harbor Perspectives in Medicine·Heath D SchmidtGhazaleh Sadri-Vakili
Feb 23, 2013·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Eric J Nestler
Sep 25, 2014·Annual Review of Psychology·Heather A Cameron, Lucas R Glover

❮ Previous
Next ❯

Citations

Jul 19, 2016·Chemical Reviews·Mahmoud LabibShana O Kelley
Aug 21, 2016·Chemico-biological Interactions·N E ScholpaB S Cummings
Sep 12, 2018·Molecular Genetics and Genomics : MGG·Xiaoyong PanYu-Dong Cai
Oct 27, 2018·Journal of Chemical Neuroanatomy·Sumitra PatiBrian S Cummings

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.