Deletion of Prkcz increases intermittent ethanol consumption in mice.

Background: Prkcz has been identified as a gene whose expression is positively correlated with ethanol (EtOH) consumption in mice and is also induced by EtOH. Two proteins are produced from Prkcz: protein kinase M zeta (PKMζ), which is expressed in the nervous system and protein kinase C zeta (PKCζ), which is expressed in other tissues. We examined Prkcz(-/-) mice that lack PKCζ and PKMζ to investigate the role of this gene in behavioral responses to EtOH.

Prkcz null mice show normal learning and memory.

Protein kinase M-ζ (PKM-ζ) is a constitutively active form of atypical protein kinase C that is exclusively expressed in the brain and implicated in the maintenance of long-term memory. Most studies that support a role for PKM-ζ in memory maintenance have used pharmacological PKM-ζ inhibitors such as the myristoylated zeta inhibitory peptide (ZIP) or chelerythrine. Here we use a genetic approach and target exon 9 of the Prkcz gene to generate mice that lack both protein kinase C-ζ (PKC-ζ) and PKM-ζ (Prkcz(-/-) mice).

JNK pathway activation is controlled by Tao/TAOK3 to modulate ethanol sensitivity.

Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures.

Responses to ethanol in C57BL/6 versus C57BL/6 × 129 hybrid mice.

Although genetic background alters responses to ethanol, there has not yet been a methodical quantification of differences in ethanol-related behaviors between inbred and hybrid mice commonly used in gene-targeting studies. Here, we compared C57BL/6NTac × 129S6/SvEvTac F1 hybrid mice (B6129S6) with C57BL/6NTac inbred mice (B6NT), and C57BL/6J × 129X1/SvJ (B6129X1) and C57BL/6J × 129S4/SvJae F1 hybrids (B6129S4) with C57BL/6J mice (B6J), in five commonly used tests: continuous access two-bottle choice drinking, intermittent limited-access binge drinking, ethanol clearance, ethanol-induced loss of the righting reflex, and conditioned place preference (CPP) for ethanol. We found that inbred B6J and B6NT mice showed greater ethanol preference and consumption than their respective hybrids when ethanol was continuously available.