Methylazoxymethanol acetate cortical hypoplasia alters the pattern of stimulation-induced behavior in neonatal rats.
In an attempt to identify a neural basis for the developmental progression in the organization of behavior evidenced in responses to lateral hypothalamic electrical stimulation, the responses to medial forebrain bundle (MFB) stimulation of pups whose mothers had been treated with saline or the antimitotic agent methylazoxymethanol acetate (MAM) on gestational Day 15 were measured. Administration of MAM at this age produces a severe and lasting cortical hypoplasia. Monopolar stainless-steel electrodes aimed at the MFB at the level of the lateral hypothalamus were implanted in pups 3, 10, 15 and 20 days of age and responses to 500 ms trains of stimulation were recorded. At 3 and 10 days of age, the number of behavioral responses increased with increasing frequency of stimulation in both MAM and saline-treated pups. Ten-day-old MAM-treated pups, however, displayed 'significantly less behavioral organization in their pattern of responding to stimulation. MAM pups, unlike saline-treated pups, continued to respond to stimulation at Day 15. Even at postnatal Day 20 some MAM-treated pups responded to stimulation. Neurochemical analysis of the brains of littermates demonstrated a significant increase in choline acetyltransferase levels indicating a relative hyperinnervation of afferent cholinergic terminals, confirming the cortical hypoplasia and replicating earlier work. These results suggest a role for the developing neocortex in organizing the behavioral responses to stimulation. The onset of cortical inhibitory mechanisms may channel behavioral responses in normally developing pups and prevent the characteristic activational responses to stimulation in Day-15 pups.
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001391:Azo Compounds / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004558:Electric Stimulation; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008474:Medial Forebrain Bundle / Q000502:physiology; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology*; D009434:Neural Pathways / Q000502:physiology; D051381:Rats
D001391:Azo Compounds; D008746:Methylazoxymethanol Acetate; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C030667:methylazoxymethanol