Submissive behavior in mice as a test for antidepressant drug activity.

Previously, with the administration of antidepressant drugs, it has been demonstrated that the rat model of clinical depression, known as the reduction of submissive behavior model (RSBM), has considerable validity. The present study is an attempt to extend the model to mice. Several antidepressant drugs as well as a number of non-antidepressant agents were administered to mice that had been identified as submissive in a behavioral testing situation.

Status of complementary and alternative medicine in the osteopathic medical school curriculum.

Reflecting society's interest in complementary and alternative medicine (CAM), most allopathic medical schools in the United States offer instruction in CAM. Pertinent information about the teaching of CAM at osteopathic medical schools is lacking. The authors therefore sought to document the form and content of CAM instruction at osteopathic medical schools and compare their findings with those reported for allopathic medical schools in a recently published survey.

Irreversible inhibition of [3H]glycine transport into channel catfish erythrocytes by thiol group modifiers.

Erythrocytes can take up amino acids from the blood by using a variety of transport systems. GLYT is a key transport protein in the plasma membrane responsible for the Na(2+)-dependent uptake of glycine needed for glutathione biosynthesis. Certain cysteine-specific compounds, particularly mercuric chloride and 5,5'-dithiobis(2-nitrobenzoate), irreversibly inhibited the [(3)H]glycine transport via GLYT by red blood cells isolated from channel catfish.

Central GABAergic systems and depressive illness.

Clinical depression and other mood disorders are relatively common mental illnesses but therapy for a substantial number of patients is unsatisfactory. For many years clinicians and neuroscientists believed that the evidence pointed toward alterations in brain monoamine function as the underlying cause of depression. This point of view is still valid.

Action of 4-amino-2-fluorobutanoic acid and other structural analogues on gamma-aminobutyric acid transport by channel catfish brain.

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in mammalian brain. The synaptic action of GABA is terminated by a sodium- and chloride-linked transport system. The GABA transporter is known as GAT and several isoforms have been identified.

Membrane glycine transport proteins.

Structurally, the simplest amino acid is glycine, and it has a number of important yet distinct functions in the body. This review focuses on the different transport systems and the associated carrier proteins for glycine that are responsible for its movement across biological membranes. Transport proteins in the class GLYT appear to be the most specific for glycine.

The teaching of complementary and alternative medicine in U.S. medical schools: a survey of course directors.

Purpose: The number of U.S. medical schools offering courses in complementary and alternative medicine (CAM) has risen sharply in recent years.

Kinetics of binding of [(3)H]glycine to transport proteins in channel catfish brain.

[(3)H]Glycine was observed to bind to channel catfish brain particles in a manner displaying saturation kinetics. The dissociation constant was calculated to be 7.38 +/- 2.

Gamma-Hydroxybutyrate (orphan medical).

Orphan Medical is developing gamma-hydroxybutyrate (Xyrem) for the potential treatment of narcolepsy [183352]. In October 2000, an NDA was filed with the FDA [384422], [405504] and Xyrem received an FDA approvable letter in July 2001. Orphan Medical stated that it believed it could meet the requirements in the letter, including a trial in respiratory-compromised patients, by the end of 2001 [414461].

Kinetics of inactivation of glutamate decarboxylase by cysteine-specific reagents.

Mercuric chloride, p-chloromercuribenzoate and 5,5'-dithiobis(2-nitrobenzoic acid) irreversibly inhibited the activity of Escherichia coli glutamate decarboxylase. Their second order rate constants for inactivation are 0.463 microM(-1) min(-1), 0.

Uptake of [(3)H]glycine by synaptosomes of channel.

It is known that channel catfish erythrocytes can take up glycine by several distinct transport systems. Further, glycine is an inhibitory neurotransmitter in mammalian brain and spinal cord. Consequently, the uptake of [(3)H]glycine by catfish brain was investigated and found to be a saturable process, dependent on the presence of Na(++) and Cl(--) and sensitive to temperature.

Actions of sodium valproate on the central nervous system.

The branched chain fatty acid, valproate, has a number of distinct pharmacological effects on the central nervous system. In experimental animals it showed clear anticonvulsant activity, an observation which led to its major clinical use as an antiepileptic agent, especially in petit mal seizures. More recently, valproate has shown its usefulness in treating mood disorders and migraine headaches.

Effects of treatment with GABA(A) receptor subunit antisense oligodeoxynucleotides on GABA-stimulated 36Cl- influx in the rat cerebral cortex.

GABA(A) receptor function was studied in cerebral cortical vesicles prepared from rats after intracerebroventricular microinjections of antisense oligodeoxynucleotides (aODNs) for alpha1, gamma2, beta1, beta2 subunits. GABA(A) receptor alpha1 subunit aODNs decreased alpha1 subunit mRNA by 59+/-10%. Specific [3H]GABA binding was decreased by alpha1 or beta2 subunit aODNs (to 63+/-3% and 64+/-9%, respectively) but not changed by gamma2 subunit aODNs (94+/-5%).

The GABA(A) receptor complex as a target for fluoxetine action.

The clinically important antidepressant fluoxetine is established as a selective serotonin reuptake inhibitor. This study demonstrates that fluoxetine also interacts with the GABA(A) receptor complex. At concentrations above 10 microM fluoxetine inhibited the binding of both [3H]GABA (IC50 = 2 mM) and [3H]flunitrazepam (IC50 = 132 microM) to the GABA(A) receptor complex in brain cortical membranes.

Pharmacology and function of imidazole 4-acetic acid in brain.

1. Imidazole 4-acetic acid (IMA) is a naturally occurring metabolite in brain, although it is unclear what biochemical pathways are involved in its biosynthesis and breakdown. Some evidence, however, suggests that IMA is an oxidation product of histamine.

Chemical inactivation of bacterial GABA aminotransferase.

The effects of three potential irreversible inhibitors of gamma-aminobutyrate aminotransferase from Pseudomonas fluorescens were studied in order to throw more light on the nature of the active site of the enzyme. The thiol group reagent mercuric chloride inactivated the enzyme in a concentration-dependent manner. Inhibition kinetics were consistent with a simple bimolecular reaction.

Inhibitors of synaptosomal gamma-hydroxybutyrate transport.

Synaptosomes prepared from mouse brain possess a Na+-dependent transport system for gamma-hydroxybutyrate displaying saturation kinetics, the transport constant (Kt) for which was calculated as 31 +/- 9 micromol/l. Several gamma-hydroxybutyrate and gamma-aminobutyric acid (GABA) structural analogues were tested as potential inhibitors of gamma-hydroxybutyrate transport. The most effective inhibitor was harmaline (Ki = 94 +/- 21 micromol/l), a known competitive inhibitor of Na+ binding to certain transport proteins.

Sites of action of gamma-hydroxybutyrate (GHB)--a neuroactive drug with abuse potential.

Objective: This review highlights the biochemistry, pharmacology, and toxicology of the naturally-occurring fatty acid derivative, gamma-hydroxybutyrate (GHB). GHB is derived from gamma-aminobutyric acid (GABA) and is proposed to function as an inhibitory chemical transmitter in the central nervous system.

Content: When administered in pharmacological doses, its powerful central nervous system depressant effects are readily observed.

Basis of the antiseizure action of phenytoin.

1. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy, for over 50 years. Its mechanism of action, however, is still open to interpretation.

Effects of repeated doses of azapirones on rat brain 5-HT1A receptors and plasma corticosterone levels.

Chronic buspirone or ipsapirone (3 mg/kg, twice daily) administration to rats for 10 days decreased the sensitivity of inhibition of single-unit activity of serotonergic dorsal raphe neurons to a challenge by each drug. The ED50 for buspirone was increased from 0.1 mg/kg to 1.

Regulation of rabbit erythrocyte Ca(2+)-pump sensitivity to calmodulin in experimental hyperlipidemia.

Intracellular free calcium activity is in part determined by a calmodulin-regulated plasma membrane Ca(2+)-pump. Since changes in Ca2+ permeability have been implicated in atherosclerotic plaque formation, we initiated a lipid hyperalimentation protocol during which we measured various erythrocyte calcium flux parameters and early atheroma development. Adolescent New Zealand White rabbits were fed a diet with 0.

Chemical modification of bacterial 4-aminobutyrate aminotransferase by phenylglyoxal.

4-Aminobutyrate aminotransferase (EC 2.6.1.

Stimulation of mouse brain gamma-hydroxybutyric acid transport by pyridoxal 5'-phosphate.

A synaptosomal preparation from mouse brain transported gamma-hydroxybutyric acid in a manner displaying saturation kinetics. A Kt of 48 +/- 11 microM was calculated. In the presence of pyridoxal 5'-phosphate, uptake was markedly enhanced.

Amino acid transport by human erythrocyte membranes.

The human erythrocyte plasma membrane is permeable to several free amino acids usually present in the bloodstream. Seven distinct routes of entry have been described which represent both secondary active transport and facilitated diffusion (passive transport). Additionally, certain amino acids can enter the cell by simple diffusion, at least to a limited extent.