THE PERIPHERAL BENZODIAZEPINE RECEPTOR IS A SENSITIVE INDICATOR OF DOMOIC ACID NEUROTOXICITY

To evaluate the utility of the peripheral benzodiazepine receptor (PER ) as a biomarker of neurotoxicity, we measured receptor levels after s ub-seizure doses of domoic acid (0-3.0 mg/kg) in rats using [H-3]PK-11 195 autoradiography. PER expression in limbic structures was significa ntly increased 5 days, but not 24 or 48 h after injection of 3.0 mg/kg domoic acid. The lar est increase in [H-3]PK-11195 binding (>500% abo ve control) was found in the CA3 subfield of the hippocampus. Other li mbic structures including the CA1 hippocampal subfield, subiculum, den tate gyrus and amygdala also showed significant increases in PER expre ssion, as did the striatum and substantia nigra pars reticulata. Small er but significant increases were also observed 5 days after injection of 1.5 mg/kg, but not in animals treated with 0.75 mg/kg domoic acid. No pathology was observed after routine histological staining of brai n tissue. Spatial learning and memory, a process thought to be associa ted with the hippocampus, was assessed in the Morris water maze. Group s treated with 1.5 and 3.0 mg/kg, but not 0.75 mg/kg domoic acid were significantly impaired in water maze performance. These findings sugge st that the PER could provide a sensitive and specific biomarker of ne urotoxicity. (C) 1997 Elsevier Science B.V.