[3H]-flunitrazepam-labeled benzodiazepine binding sites in the hippocampal formation in autism: a multiple concentration autoradiographic study.
Increasing evidence indicates that the GABAergic system in cerebellar and limbic structures is affected in autism. We extended our previous study that found reduced [(3)H]flunitrazepam-labeled benzodiazepine sites in the autistic hippocampus to determine whether this reduction was due to a decrease in binding site number (B (max)) or altered affinity (K (d)) to bind to the ligand. Quantitation of hippocampal lamina demonstrated a 20% reduction in B (max) indicating a trend toward a decreased number of benzodiazepine binding sites in the autistic group but normal K (d) values. A reduction in the number of hippocampal benzodiazepine binding sites suggests alterations in the modulation of GABA(A) receptors in the presence of GABA in the autistic brain, possibly resulting in altered inhibitory functioning of hippocampal circuitry.
Guptill
Jeffrey T
JT
Department of Anatomy and Neurobiology, Boston University School of Medicine, 715 Albany Street, R-1003, Boston, MA 02118, USA.
Booker
Anne B
AB
Gibbs
Terrell T
TT
Kemper
Thomas L
TL
Bauman
Margaret L
ML
Blatt
Gene J
GJ
D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000175:diagnosis* / Q000473:pathology*; D001345:Autoradiography / Q000295:instrumentation; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D001665:Binding Sites / Q000187:drug effects; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D005445:Flunitrazepam / Q000493:pharmacokinetics*; D018757:GABA Modulators / Q000493:pharmacokinetics*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000378:metabolism* / Q000473:pathology*; D009562:Nissl Bodies / Q000378:metabolism / Q000473:pathology; D018079:Receptors, GABA / Q000378:metabolism
D018757:GABA Modulators; D018079:Receptors, GABA; D001569:Benzodiazepines; D005445:Flunitrazepam