beta-Amyloid 25-35 and/or quinolinic acid injections into the basal forebrain of young male Fischer-344 rats: behavioral, neurochemical and histological effects.
beta-Amyloid peptides have been shown to potentiate the neurotoxic effect of excitatory amino acids in vitro. In order to determine if this occurs in vivo, four experiments were performed. We injected beta-amyloid 25-35 (beta A 25-35) and/or quinolinic acid (QA) bilaterally into the ventral pallidum/substantia innominata (VP/SI) of rats. Control rats received vehicle infusions. A high dose of QA (75.0 nmol/3 microliters) increased open field activity and impaired spatial learning in the Morris water maze, but did not affect the acquisition of a one-way conditioned avoidance response. These changes were associated with histological evidence of neurotoxicity and a reduction in amygdaloid but not frontal cortical or hippocampal choline acetyltransferase (ChAT) activity. A lower dose of QA (37.5 nmol/3 microliters) produced no behavioral effects. It reduced amygdaloid ChAT activity to a lesser extent than the higher dose (15% vs. 29-37%), and caused less histological damage. beta A 25-35 (1.0 or 8.0 nmol/3 microliters) failed to produce behavioral, histological or neurochemical signs of toxicity. Neither dose of beta A 25-35 potentiated the effects of QA (37.5 nmol) on behavior or amygdaloid ChAT activity, and did not appear to increase the histological damage caused by QA. These results suggest that in vivo beta A 25-35 is not neurotoxic and does not potentiate the neurotoxicity of QA in the VP/SI. Further, the histological effects of a high dose of beta A 25-35 (8.0 nmol/3 microliters; a cavitation containing a Congo red positive proteinaceous material) are quite distinct from those produced by a high dose of QA (75.0 nmol/3 microliters; widespread neuronal loss and gliosis).
Sigurdsson
E M
EM
Department of Pharmacology, Loyola University Chicago Medical Center, Maywood, IL 60153, USA.
Hejna
M J
MJ
Lee
J M
JM
Lorens
S A
SA
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D016548:Prosencephalon / Q000033:anatomy & histology / Q000502:physiology*; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D002795:Choline O-Acetyltransferase; D017378:Quinolinic Acid