Antisense oligonucleotide to GABAA receptor gamma 2 subunit induces loss of neurones in rat hippocampus.

The binding site for 1,4-benzodiazepines in the brain is part of the hetero-oligomeric gamma-aminobutyric acid (GABA)A receptor complex which regulates a chloride ion channel. The presence of the gamma 2 subunit in the complex is necessary for the binding of benzodiazepines to their binding site. This study demonstrates a reduction of benzodiazepine receptor radioligand binding by 43% compared to control following infusion of phosphorothioate antisense oligodeoxynucleotide to gamma 2 subunit into rat hippocampus.

New diagnostic vistas.

There are many difficulties in establishing criteria for better drug compliance and improved quality assurance in the treatment of schizophrenic patients. The most serious problem (especially with first episodes) is that of diagnosis. Since no biological markers for schizophrenia have been found the clinician is referred to "symptom collecting"--including collecting social data.

Calcium homeostasis in fibroblasts from patients with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disorder of the motor system in the CNS characterized by motor neuron death in the spinal cord, brain stem and cortex. Readily available tissues such as fibroblasts from ALS patients can serve as simple model systems to study the molecular mechanisms leading to degenerative disorders. We have used Fura-2 fluorescence microscopy and single-cell imaging to study the spatiotemporal dynamics of intracellular free calcium ([Ca2+]i) in primary cultures of fibroblasts from skin biopsies from ALS and normal subjects.

Differential modulation of brain benzodiazepine receptor subtypes by ricinelaidic acid in vitro.

The C-18 hydroxy fatty acids ricinelaidic acid and ricinoleic acid diminish the oleic acid-stimulated agonist benzodiazepine binding in the rat brain in vitro. The oleic acid-induced enhancement of [3H]diazepam binding was completely abolished in membranes from the cerebellum, but only partially decreased in membranes from the hippocampus, cortex and the whole brain from 7-day-old rat pups. Related hydroxy fatty acids as well as hydroxy fatty acid esters had no effect on the oleic acid-stimulated diazepam receptor binding.

Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol.

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability.

Effect of chronic treatment with NNC 756, a new D-1 receptor antagonist, or raclopride, a D-2 receptor antagonist, in drug-naive Cebus monkeys: dystonia, dyskinesia and D-1/D-2 supersensitivity.

When given subcutaneously in gradually increasing doses, up to 1 mg/kg, NNC 756, a dopamine (DA) D-1 antagonist, failed to produce dystonia in eight drug-naive Cebus monkeys. In contrast, raclopride, a DA D-2 antagonist, produced dystonia at low doses (0.010-0.

Cerebrospinal fluid concentrations of neuropeptide Y in depressed patients and in controls.

Concentrations of Neuropeptide Y-like (NPY-LI) immunoreactivity in cerebrospinal fluid (CSF) were measured in a group of depressed patients (n = 24) and compared with that of control subjects (n = 12). CSF-NPY-LI was significantly reduced in the group of non-endogenously depressed patients when classified according to Newcastle Rating Scale for Depression--1971 (N-II). No significant correlation was found in the control or depressed groups between lumbar concentrations of NPY-LI and a number of other neurotransmitters.