Advances in information concerning brain function in animals and advances in analytical neurochemical methods for determining extremely low levels of compounds in physiological fluids have opened great opportunities for clinical neurochemical studies of autism. Nevertheless, the behavioral deficits in autistic individuals are major obstacles to clarification of the relations between symptoms and biochemical dysfunction in the brain. The fundamental preclinical and clinical studies of serotonin, dopamine, and norepinephrine metabolism related to infantile autism are reviewed, and new studies are suggested as examples of the productive strategies that will illuminate features of the autistic syndrome in the next decade.
The relative contribution of dopamine (DA) and norepinephrine (NE) in behavioral arousal was examined in developing rat pups using intracisternal 6-hydroxydopamine (6-OHDA) either alone or following pretreatment with desmethylimipramine (DMI). Such treatments were designed to examine the effects of preferential reduction of DA (DA depletion), NE (NE depletion), or both catecholamines (CA depletion) in the development of motor activity and escape performance. General motor activity increased with age and, over all ages, DA-depleted pups tended to exhibit greater activity. This was most apparent at 15 days of age, where DA-depleted pups were significantly more active than controls, NE-depleted, or CA-depleted pups. DA-depleted pups failed to exhibit the steep decline in activity over time (habituation of activity) demonstrated by the control and NE-depleted pups, while pups depleted of both CA fell into an intermediate position in habituation. Escape latency in a T-maze at 20 days and shuttle box at 26 days of age indicated comparable performance to controls for NE-depleted pups, while those animals in DA-depleted and CA-depleted groups appeared unable to perform the task. Brain CA concentrations (determined by a radioenzymatic assay) indicated preferential reduction of DA in the DA-depleted group to concentrations 25% of controls, reduction of NE to 62% of controls in the NE-depleted group, and reductions of DA to 42% and NE to 60% in the CA-depleted group. These results suggest that preferential reduction of brain DA in the developing rat pup increases motor activity and impairs habituation of activity during the stage of behavioral arousal in week 3 of postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)
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