PKMζ in the nucleus accumbens acts to dampen cocaine seeking

The constitutively active, atypical protein kinase C, protein kinase M-ζ (PKMζ), is exclusively expressed in the brain and its expression increases following exposure to drugs of abuse. However, the limitations of currently available tools have made it difficult to examine the role of PKMζ in cocain...

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Bibliographic Details
Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2018-11, Vol.43 (12), p.2390-2398
Main Authors: McGrath, Anna G, Lenz, Jeffrey D, Briand, Lisa A
Format: Article
Language:English
Subjects:
Animals
Cocaine
Cocaine - administration & dosage
Dopamine Uptake Inhibitors - administration & dosage
Drug abuse
Drug self-administration
Female
Females
Food
Gene Deletion
Kinases
Male
Males
Mice
Mice, Inbred C57BL
Mice, Knockout
Narcotics
Nucleus accumbens
Nucleus Accumbens - drug effects
Nucleus Accumbens - enzymology
Protein kinase C
Protein Kinase C - deficiency
Protein Kinase C - genetics
Reinforcement
Reinstatement
Rodents
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Summary:The constitutively active, atypical protein kinase C, protein kinase M-ζ (PKMζ), is exclusively expressed in the brain and its expression increases following exposure to drugs of abuse. However, the limitations of currently available tools have made it difficult to examine the role of PKMζ in cocaine self-administration and relapse. The current study demonstrates that constitutive deletion of PKMζ potentiates cue-induced reinstatement of cocaine seeking and increases both food and cocaine self-administration, without affecting cue-driven food seeking in both male and female mice. Conditional deletion of PKMζ within the nucleus accumbens recapitulated the increase in cocaine taking and seeking seen in the constitutive knockout mice, but only in male animals. Site-specific knockdown of PKMζ in the nucleus accumbens had no effect on cocaine taking or seeking in female mice. Additionally, neither male nor female mice exhibited any alterations in food self-administration or cue-induced reinstatement of food seeking following accumbal deletion of PKMζ. Taken together these results indicate that PKMζ may act to dampen cocaine taking and seeking. Furthermore, these results indicate that PKMζ is playing divergent roles in reward seeking in males and females.
ISSN:0893-133X
1740-634X
DOI:10.1038/s41386-018-0170-1