Session 4: Neurotransmitters Systems in Autism

P. Whitaker-Azmitia

Understanding the causes of autism, and proposing effective treatment strategies, could be greatly advanced by the establishment of an animal model. The current work is aimed at producing such a model, by treating developing rat pups with a serotonergic agonist, 5-methoxytryptamine (5-MT ; 1 mg/kg) during development (from gestational age 12 days to postnatal day 20), thus mimicking one of the hallmark neurochemical features of the illness - increases in the neurotransmitter serotonin. Animals were tested in behavioral paradigms which may resemble the human illness. Treated rat pups were found to be overeactive to auditory or tactile sensory stimuli, to display changes in the negative geotaxic test of motor development, to show lack of separation-induced vocalizations when their dam was removed and to show increased perseveration in the spontaneous alternation task. As well, the animals showed metabolic changes in brain activity, using in vivo magnetic resonance spectroscopy, which are consistent with those observed in autistic children. Preliminary morphological characterization of the brains indicates altered development of the amygdala (using CGRP immunostaining) and sensory cortices, as well as a loss of serotonin terminals. In summary, the model we are proposing shows some of the behavioral and metabolic features of autism, as well as being produced through alteration of a neurochemical system known to be altered in autism.

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