PKMζ in the nucleus accumbens acts to dampen cocaine seeking

The constitutively active, atypical protein kinase C, protein kinase M-{zeta} (PKM{zeta}), 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 PKM{zeta} in cocaine addiction. The current study demonstrates that constitutive deletion of PKM{zeta} potentiates cue-induced reinstatement of cocaine seeking and increases both food and cocaine taking, without affecting cue-driven food seeking in both male and female mice. Conditional deletion of PKM{zeta} 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 PKM{zeta} in the nucleus accumbens had no effect on cocaine or natural reward behaviors in female mice. Taken together these results indicate that PKM{zeta} may act to dampen addictive phenotypes. Furthermore, these results indicate that PKM{zeta} is playing divergent roles in reward seeking in males and females.