Behavioral and magnetic resonance spectroscopic studies in the rat hyperserotonemic model of autism.
Autism is classified as a pervasive developmental disorder, with several cardinal features including sensory disturbances, obsessive-compulsive-like behavior, lack of bonding to caregivers and motor disturbances. To date, there is a lack of an animal model of the disease. 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 then tested in behavioral paradigms that may resemble the human illness. Treated rat pups were found to be overreactive 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 decreased alternation in the spontaneous alternation task. As well, the animals showed metabolic abnormalities in the brain using in vivo proton magnetic resonance spectroscopy, which are consistent with those observed in autistic children. 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.
Kahne
David
D
Department of Psychology, SUNY at Stony Brook, 11794-2500, USA.
Tudorica
Alina
A
Borella
Alice
A
Shapiro
Lee
L
Johnstone
Fabian
F
Huang
Wei
W
Whitaker-Azmitia
Patricia M
PM
D008735:5-Methoxytryptamine / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000818:Animals; D001321:Autistic Disorder / Q000378:metabolism / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D001724:Birth Weight / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D010812:Physical Stimulation; D004856:Postural Balance / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014828:Vocalization, Animal / Q000187:drug effects
D017366:Serotonin Receptor Agonists; D012701:Serotonin; D008735:5-Methoxytryptamine