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.

中文翻译：

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伏伏核中的PKMζ起到抑制可卡因搜寻的作用。

组成型活性非典型蛋白激酶C蛋白激酶M-ζ（PKMζ）仅在大脑中表达，暴露于滥用药物后其表达增加。但是，当前可用工具的局限性使得很难检查PKMζ在可卡因自我管理和复发中的作用。当前的研究表明，PKMζ的组成型缺失可增强提示诱导的可卡因寻找的恢复，并增加食物和可卡因的自我给药，而不会影响雄性和雌性小鼠的提示驱动的寻找食物。伏伏核内PKMζ的有条件缺失概括了在组成型敲除小鼠中可卡因的摄取和寻找的增加，但仅在雄性动物中可见。伏隔核中PKMζ的位点特异性敲低对雌性小鼠中可卡因的摄取或寻找没有影响。另外，雄性和雌性小鼠均未显示出食物自我给药的任何改变或提示性地因PKMζ的缺失而寻求的食物诱导的恢复。这些结果加在一起表明，PKMζ可能会抑制可卡因的摄取和寻找。此外，这些结果表明，PKMζ在男性和女性的报酬寻求中扮演着不同的角色。