We provide evidence that normal human presenilins can substitute for Caenorhabditis elegans SEL-12 protein in functional assays in vivo. In addition, six familial Alzheimer disease-linked mutant human presenilins were tested and found to have reduced ability to rescue the sel-12 mutant phenotype, suggesting that they have lower than normal presenilin activity. A human presenilin 1 deletion variant that fails to be proteolytically processed and a mutant SEL-12 protein that lacks the C terminus display considerable activity in this assay, suggesting that neither presenilin proteolysis nor the C terminus is absolutely required for normal presenilin function. We also show that sel-12 is expressed in most neural and nonneural cell types in all developmental stages. The reduced activity of mutant presenilins and as yet unknown gain-of-function properties may be a contributing factor in the development of Alzheimer disease.

The question of whether opiates stimulate feeding by enhancing taste pleasure was investigated by examining the effect of morphine upon hedonic and aversive reactions to taste (tongue protrusions, gapes, etc.). Rats (n = 12) were given SC injections of morphine (4 mg/kg) or equal volumes of isotonic saline 2 h after the start of their daily light cycle. Food intake was measured in a 2-h test. On days when they were given morphine, rats ate significantly more food than when given saline. Hedonic and aversive taste reactions were elicited by an infusion of sucrose-quinine solution into the mouth and were measured subsequently in a slow-motion video analysis. The same rats that showed an increase in food intake after treatment with morphine showed a significant increase in their positive hedonic responses. Aversive reactions were unchanged by morphine. The results support the hypothesis that morphine enhances feeding by increasing the hedonic palatability of food.

LIN-12 and GLP-1 are members of the LIN-12͞Notch family of receptors that mediate cell-cell interactions during development. The sel-8 gene had been identified previously in a screen for suppressors of a mutation that constitutively activates LIN-12. Here, we report that sel-8 is essential for lin-12-and glp-1-mediated signaling, and that SEL-8 is a glutamine-rich nuclear protein. We postulate that SEL-8 serves as a transcriptional coactivator or as an assembly factor for transcription complexes that contain the LIN-12 or GLP-1 intracellular domains.