Prolonged swim-test immobility of serotonin N-acetyltransferase (AANAT)-mutant mice

Serotonin N-acetyltransferase (AANAT; EC 2.3.1.87) metabolizes serotonin in to N-acetylserotonin (NAS). AANAT mRNA is expressed in the pineal gland and retina, and also in the rat brain. It was proposed that NAS could be a med iator of the antidepressant action of drugs, and it was shown that chronic but not acute treatment of rats with the antidepressant fluoxetine increase s the content of AANAT mRNA in the rat hippocampus. Consequently, AANAT def iciency might be involved in the pathobiology of depression. C57BL/6J mice have a mutant AANAT gene and are considered AANAT-deficient, i.e., "knocked down" (compared with their normal counterparts, C3H/HeJ mice). In this stu dy, we investigated whether AANAT mRNA is expressed in the brain of C57BL/6 J and C3H/HeJ mice and whether those mice differ behaviorally, i.e., in a f orced swimming test which is used to evaluate antidepressant drugs (such dr ugs shorten the time of immobility). We found that C3H/HeJ mice express in the brain normal AANAT mRNA, whereas C57BL/6J mice express mutated AANAT mR NA. The mutant, AANAT knocked down C57BL/6J mice displayed significantly lo nger times of immobility ("depression"). This difference was evident regard less of the circadian rhythm, i.e., both during the day and in the dark at night. Further studies are needed to fully characterize the behavioral sign ificance of AANAT mutation and its possible link to depression.