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PKMζ in the nucleus accumbens acts to dampen cocaine seeking
- Source :
- Neuropsychopharmacology. 43:2390-2398
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Drugs of abuse
media_common.quotation_subject
Constitutively active
Biology
Nucleus accumbens
Nucleus Accumbens
Mice
03 medical and health sciences
0302 clinical medicine
Cocaine
Dopamine Uptake Inhibitors
Animals
Protein kinase A
Protein Kinase C
030304 developmental biology
media_common
Mice, Knockout
Pharmacology
0303 health sciences
Gene knockdown
Addiction
Research Highlight
Atypical protein kinase C
Mice, Inbred C57BL
Psychiatry and Mental health
030104 developmental biology
Knockout mouse
Female
Neuroscience
Gene Deletion
030217 neurology & neurosurgery
Cocaine seeking
Subjects
Details
- ISSN :
- 1740634X and 0893133X
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....349476c72b56cdebf13eb26164252ede