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Preventing relapse to drug use is a major challenge for the treatment of drug addiction. Environmental cues are among the major determinants of relapse in abstinent cocaine users. The protein kinase M ζ (PKMζ) is involved in the generation and maintenance of long-term potentiation and is critical in memory storage. Here we show that inhibition of PKMζ in the nucleus accumbens (NAc) shell, a major component of the reward system that plays an important role in mediating drug craving and relapse, by a selective inhibitor ζ inhibitory peptide (ZIP), abolished cocaine-induced conditioned place preference (CPP). However, the injection of ZIP into the NAc core resulted in earlier onset of CPP extinction. Finally, we found that the levels of PKMζ and GluR2 in the NAc remained unchanged, while the GluR1 levels were elevated following CPP and fully reversed by ZIP injection. Together, our results suggest that inactivation of PKMζ in the NAc may result in the dissociation between the rewarding properties of the drug and the drug-related environment and may serve as a novel target for the treatment of drug relapse. [ABSTRACT FROM AUTHOR]

Early blindness in humans and experimental visual deprivation in animal models are known to induce compensatory somatosensory and/or auditory activation of the visual cortex. An abnormal hydrocephalic cat with extreme malformation of the visual system, born in our breeding colony, rendered a good model system for investigating possible cross-modal compensation in such a pathological case. For comparison, we used normal and neonatally enucleated cats. When introduced to a novel environment, the abnormal cat behaved as if it was completely blind, yet it responded normally to auditory stimuli. As anticipated, single cells in the visual cortex of normal cats responded to visual, but not to auditory stimuli. In the visual cortex of enucleated cats, flashes of light did not elicit field-evoked potentials or single-unit responses. However, several cells did respond to various auditory stimuli. In the remnant visual cortex of the abnormal cat, auditory stimuli evoked field potentials and single-cell responses. Unexpectedly, however, unlike the enucleated cats, in the abnormal cat, flashes of light also elicited field-evoked potentials. Judging by its behavior, it is very likely that this deformed cat had completely lost its ability to perceive images, but had probably retained some sensitivity to light. [ABSTRACT FROM AUTHOR]