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1.
Mol Psychiatry ; 15(5): 512-22, 446, 2010 May.
Article in English | MEDLINE | ID: mdl-19721434

ABSTRACT

A powerful convergence of genetics, neuroimaging and epidemiological research has identified the biological pathways mediating individual differences in complex behavioral processes and the related risk for disease. Orthologous genetic variation in non-human primates (NHPs) represents a unique opportunity to characterize the detailed molecular and cellular mechanisms that bias behaviorally and clinically relevant brain function. We report that a rhesus macaque orthologue of a common polymorphism of the serotonin transporter gene (rh5-HTTLPR) has strikingly similar effects on behavior and brain morphology to those in humans. Specifically, the rh5-HTTLPR (S)hort allele broadly affects cognitive choice behavior and brain morphology without observably affecting the 5-hydroxytryptamine (5-HT) transporter or 5-HT(1A) concentrations in vivo. Collectively, our findings indicate that 5-HTTLPR-associated behavioral effects reflect genotype-dependent biases in cortical development rather than static differences in serotonergic signaling mechanisms. Moreover, these data highlight the vast potential of NHP models in advancing our understanding of human genetic variation affecting behavior and neuropsychiatric disease liability.


Subject(s)
Choice Behavior/physiology , Cognition/physiology , Polymorphism, Genetic/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin/metabolism , Synaptic Transmission/genetics , Animals , Avoidance Learning/physiology , Behavior, Animal/physiology , Benzylamines/metabolism , Brain/diagnostic imaging , Brain/drug effects , Brain Mapping , Carbon Isotopes/metabolism , Genotype , Macaca mulatta , Magnetic Resonance Imaging/methods , Male , Neuropsychological Tests , Piperazines/metabolism , Positron-Emission Tomography/methods , Protein Binding/drug effects , Protein Binding/genetics , Pyridines/metabolism , Receptor, Serotonin, 5-HT1A/genetics , Serotonin/genetics , Time Factors , Tritium/metabolism
2.
Anesthesiology ; 42(3): 307-11, 1975 Mar.
Article in English | MEDLINE | ID: mdl-1115385

ABSTRACT

Malignant hyperthermia in susceptible swine was completely blocked by epidural anesthesia with lidocaine. Incomplete epidural anesthesia modified the disease but did not prevent it. These studies indicate the importance of the nervous system in the triggering of malignant hyperthermia. (Key words: Hyperthermia, malignant; Anesthetic technique, peridural.).


Subject(s)
Anesthesia, Epidural , Malignant Hyperthermia/prevention & control , Anesthesia, Epidural/methods , Animals , Body Temperature , Central Nervous System/physiopathology , Female , Halothane/administration & dosage , Lidocaine , Male , Malignant Hyperthermia/chemically induced , Malignant Hyperthermia/etiology , Muscle Rigidity/chemically induced , Muscle Rigidity/etiology , Swine , Time Factors
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