Nonselective PKC inhibitors decrease CPP induced by many addictive drugs. In rats, chelerytrhine reduces cocaine-induced CPP when administered by intracerebroventricular injection125 and inhibits methamphetamine-induced CPP when administered through intra-NAc injection.180 Likewise, intra-NAc injection of NPC 15437 reduces amphetamine-induced CPP.226 It is not known which PKC isozymes regulate psychostimulant-induced CPP. Studies with PKCγ and PKCε knockout mice have revealed different roles for these isozymes in regulating morphine-induced CPP. Morphine CPP is abolished in PKCγ knockout mice,184 whereas PKCε knockout mice show CPP at low doses of morphine and more prolonged expression of morphine CPP when compared with wild-type mice.221 In contrast to morphine, low doses of ethanol do not result in CPP in PKCε knockout mice but instead cause conditioned place aversion.227 Aversion to low doses of ethanol may explain, in part, why PKCε knockout mice self-administer less ethanol than wild-type littermates. Ethanol CPP has not yet been investigated in PKCγ knockout mice.
