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Relevant to the mechanism of PKC downregulation by antidepressants and valproate (see below), acute lithium use mimics the effect of phorbol esters with resultant activation of PKC (energizing immediate early genes such as c-fos), while chronic lithium use attenuates the phorbol ester action on PKC, down-regulating the enzyme (Manji and Lenox, 1994)

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