Cyclin-dependent kinase inhibitor 1a (p21) modulates response to cocaine and motivated behaviorss

Natalie E. Scholpa, Sherri B. Briggs, John J. Wagner, Brian S. Cummings

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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, k-opioid-induced place aversion was also significantly enhanced. Concentrationdependent 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 responses to either rewarding or aversive stimuli. Collectively, these findings demonstrate a previously unreported involvement of p21 in modulating responses to cocaine and in motivated behaviors.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume357
Issue number1
DOIs
StatePublished - Apr 2016
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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