Pharmacological manipulations of anoxia-induced free fatty acid accumulation in the mouse brain.
The accumulation of free fatty acid (FFA) in the brain occurs within minutes of anoxia, induced by exposing mice to a 100% N2 atmosphere. The rate of FFA release is high within the first minute and continues to increase moderately hereafter. FFA is apparently accumulated at the highest concentration in the cerebral hemispheres. The release of FFA can be inhibited partly by CNS depressants like N6-cyclopentyladenosine, pentobarbital, ethanol, or 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3(2H)-one (THIP). Antiadrenergic compounds such as reserpine, clondine, or prazosine were also found to be active. The N2 anoxia was initially and temporarily associated with motor excitation termed fight and flight reaction. This behavior could be reduced by administration of N6-cyclopentyl-adenosine, pentobarbital, ethanol, reserpine, and prazosine, but not by THIP or clonidine. The glutamate antagonist MK-801 inhibited the fight and flight reaction, but did not affect the FFA accumulation. The data are consistent with the view that brain anoxia initially increases FFA by receptor-mediated polyphosphoinositide breakdown and that the alpha-1 adrenergic receptor is one of the receptors involved. The data also indicate that the fight and flight reaction is dissociated from the events that lead to FFA release, and may involve the stimulation of glutaminergic NMDA receptors.
Olsen
U B
UB
Department of Pharmacology, Novo Nordisk A/S, Måløv, Denmark.
Kofod
A R
AR
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001237:Asphyxia / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism*; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013565:Sympatholytics / Q000494:pharmacology*
D000777:Anesthetics; D002492:Central Nervous System Depressants; D005230:Fatty Acids, Nonesterified; D016194:Receptors, N-Methyl-D-Aspartate; D013565:Sympatholytics; D016291:Dizocilpine Maleate