ABSTRACT
Prostaglandin E1 (PGE1) and prostanoid precursor fatty acids enhance the acute sedative effects of ethanol in mice, and reduce the intensity of withdrawal after chronic exposure to ethanol. Aspirin, and other inhibitors of prostanoid synthesis, attenuate ethanol's sedative effects, and interfere with the beneficial effects of prostanoid precursors (but not of PGE1 itself) in withdrawal. Neither aspirin nor indomethacin administered alone affect withdrawal behavior. In contrast, ethanol impairment of rotorod behavior is not affected by prostanoid precursors nor by aspirin. These findings support a role for prostanoids as modulators (? mediators) of certain direct effects of ethanol and a role for prostanoid deficiency in the pathogenesis of withdrawal behavior.
Subject(s)
Alcoholism/physiopathology , Brain/physiopathology , Fatty Acids, Essential , Fatty Acids/physiology , Prostaglandins/physiology , Prostanoic Acids/physiology , Alprostadil , Animals , Aspirin , Ethanol/adverse effects , Fatty Acids, Unsaturated , Humans , Ibuprofen , Indomethacin , Linoleic Acids , Linolenic Acids , Male , Mice , Oenothera biennis , Plant Oils , Prostaglandins E , Substance Withdrawal Syndrome/physiopathology , gamma-Linolenic AcidABSTRACT
Both clinical and laboratory studies suggest that age-related memory deficits may be due, at least in part, to disturbances in muscarinic acetylcholine (mAChR) receptors. In order to further evaluate this premise, the present studies examined the electrophysiological responses rates of hippocampal pyramidal cells to iontophoretically applied ACh in young, middle-age and aged animals. The relationship between age and muscarinic agonist and antagonist binding in the hippocampus was also examined. In addition, possible age-related changes in receptor-effector coupling were assessed by determining calmodulin levels and the activities of phospholipid methyl-transferase I and II. Analysis of electrophysiological data showed selective age-related decrements in the ability of ACh to alter burst rate but not simple spike rate. These age-related decreases in the efficacy of ACh to increase burst rate were not paralleled by decreases in mAChR density as assessed by 3H-QNB binding, but they were temporally paralleled by age-related changes in the ability of oxotremorine to inhibit 3H-QNB binding. In the young animals, the resultant Hill coefficients derived from these analyses approached 1, while in the middle and old aged animals, the Hill coefficients deviated significantly from 1, indicating the possible existence of 2 or more receptor states with differential affinity for oxotremorine in the 2 older age groups. When carbamylcholine was used to inhibit 3H-QNB, these complex binding patterns were seen even in the young, since carbamylcholine induces conformational/orientational changes in the mAChR while oxotremorine does not.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Aging , Brain/physiopathology , Memory/physiology , Receptors, Muscarinic/physiology , Acetylcholine/pharmacology , Animals , Hippocampus/drug effects , Male , Methylation , Molecular Conformation , Phospholipids/metabolism , Rats , Rats, Inbred F344 , Synaptic TransmissionABSTRACT
Phospholipids in red blood cells (RBCs) of schizophrenics and controls were determined. Three different RBC preparations and two different extraction methods were used. Phospholipids were separated by thin layer chromatography and by high pressure liquid chromatography, and were quantified by phosphorus analysis and by ultraviolet absorption. Findings were consistent with values previously reported for normals. However, in contrast to recent reports of elevated phosphatidylserine levels in schizophrenics' RBCs, we observed no differences between populations.
