Introduction and history of the use of electroencephalography in animal drug studies.

A brief review of the development and the state-of-the-art of EEG methods used to study drug effects is presented. Classification systems based on drug effects in animals kept awake artificially, and based on drug effects on the sleep-wake state duration and distribution are discussed. It is concluded that the techniques are there and the time is ripe to develop animal EEG-based drug classification systems with high predictive ability.

The time course of sigma activity and slow-wave activity during NREMS in cortical and thalamic EEG of the cat during baseline and after 12 hours of wakefulness.

The extrapolation from recent neurophysiological findings concerning the dependency of spindle and slow-wave oscillations of thalamocortical neurons on membrane potential to macroscopic EEG events, predicts a reciprocal relation between spindle activity and slow-wave activity (SWA) in thalamic and cortical EEG during non-rapid-eye-movement sleep (NREMS). To test this hypothesis, the EEG recorded in 8 cats, from the nucleus centralis lateralis of the thalamus and from the skull during a 12-h baseline dark period and during a 12-h recovery dark period, following a 12-h sleep deprivation, were analyzed. Per 12-s epoch, sleep-wake behaviour was determined and spectral power density was computed in the slow-wave frequency range (0.

Enhanced slow-wave activity within NREM sleep in the cortical and subcortical EEG of the cat after sleep deprivation.

Electroencephalograms (EEGs) of the cortex and of seven subcortical structures were recorded during two baseline days and during a recovery day following a 12-hour period of sleep deprivation (SD) in eight cats. The EEGs were analyzed by visual scoring and by spectral analysis. The following subcortical structures were studied: hippocampus, amygdala, hypothalamus, nucleus centralis lateralis of the thalamus, septum, nucleus caudatus and substantia nigra.

Effects of circadian phase and duration of sleep deprivation on sleep and EEG power spectra in the cat.

The electroencephalogram (EEG) of cats was recorded under baseline conditions (LD 12:12) and after 4 and 8 h of sleep deprivation (SD). The EEG was analyzed by visual scoring and by spectral analysis. Under baseline conditions the 24-h distribution of sleep was bimodal: the smallest amounts of sleep occurred at the light-dark and dark-light transitions.

CGP 35348: a centrally active blocker of GABAB receptors.

The biochemical, electrophysiological and pharmacological properties of the new GABAB receptor blocker CGP 35348 are described. In a variety of receptor binding assays CGP 35348 showed affinity for the GABAB receptor only. CGP 35348 had an IC50 of 34 microM at the GABAB receptor.

The competitive NMDA receptor antagonists CGP 37849 and CGP 39551 are potent, orally-active anticonvulsants in rodents.

Anticonvulsant properties of CGP 37849 and CGP 39551, two novel phosphono-amino acids which are competitive NMDA receptor antagonists, were examined in rodents. At optimal pretreatment times CGP 37849 suppressed electroshock-induced seizures in mice and rats with ED50s ranging from 8 to 22 mg/kg after oral administration, and 0.4 to 2.

Effects of psychotropic drugs on the behavior and neurochemistry of olfactory bulbectomized rats.

Since its first characterization as a model for the detection of antidepressant drugs (van Riezen et al., 1976) a large body of data now supports the view that olfactory bulbectomy produces changes in animal behavior that are reversed by chronic treatment with antidepressants. The behavioral deficits seen in olfactory bulbectomized rats (such as irritability, deficits in acquisition of avoidance and of appetitive motivated conditioning and hyperactivity in a new environment) are probably the results of a reduced ability to adapt to environmental changes.

Enhanced functional responsiveness of the dopaminergic system--the mechanism of anti-immobility effects of antidepressants in the behavioural despair test in the rat.

Imipramine, desipramine, maprotiline and atypical antidepressants such as mianserin, trimipramine and levoprotiline were tested in the behavioural despair test in rats. After chronic treatment (twice daily for 7 days), all the drugs, including trimipramine and levoprotiline, significantly reduced the immobility of rats subjected to forced swimming. Of particular interest are the findings with levoprotiline, which in contrast to other antidepressant drugs did not exert any direct or indirect influence on the metabolism of catecholamines and does not seem to interact with the known receptor systems, except the H1 receptors.

Neuropeptides: ACTH-peptides in dementia.

Studies on the treatment of demented patients with ACTH neuropeptides are reviewed. The discussion is restricted to ACTH4-10 and an orally active peptide, the modified ACTH4-9 fragment: H-Met (O2)-Glu-His-Phe-D-Lys-Phe-O (Org 2766). The first part of the review concentrates on data from animal pharmacology and basic and human studies which have relevance for the clinical effects shown in demented patients.

Response changes after repeated low apomorphine: dopamine autoreceptor desensitization or learning?

Repeated injection of rats with low doses of apomorphine (APO), which selectively interact with dopamine (DA) autoreceptors, caused a change in yawning responses that suggests initial low-APO-induced desensitization of DA autoreceptors, followed by a long-lasting rebound hypersensitivity. Repeated treatment with low APO followed by open-field testing, however, yielded totally different results. APO accelerated intrasession response decrement and upon repeated administration enhanced the intersession response decrement.

[Effects of synthetic neuropeptides in psycho-organic brain syndrome. Results with ACTH4-10 and ACTH4-9-analog (author's transl)].

The effects of ACTH4-10 (Org O163) and of the ACTH4-9 analog (Org 2766) were tested in 20 male patients suffering from a mild to moderate cerebroorganic impairment. Patients were aged between 51-72 years (mean 60.9).

Pituitary hormones and amnesia.

Pituitary hormones profoundly influence behavior through direct actions on the brain. One of these behavioral effects is the attenuation of experimental amnesia. Traditionally, amnesia is considered as a "loss of memory.

The pharmacology of mianserin (Org. GB 94) Leviron, a really different antidepressant.

The new tetracyclic antidepressant mianserin was clinically shown to be better than placebo and to have less side-effects than the tricyclic antidepressants. It has neither anticholinergic activity nor is it effective in the classical tests of antidepressant activity based on amine re-uptake inhibition. Mianserin shows clear antidepressant activity in tests with muricide rats, in bulbectomised rats and in the acquired immobility test with rats or mice.

[Possible consequence of ACTH-like peptides for human mental performance (author's transl)].

ACTH affects behavior of rats. The results of the reported experiments suggest that ACTH effects on conditioned behavior are the result of an improved motivation or attention. The ACTH fragments, ACTH 4--10 and ACTH 4--9, have the behavioral effects of ACTH but are devoid of endocrine activities.

Olfactory bulb ablation in the rat: behavioural changes and their reversal by antidepressant drugs.

1. The effects of bilateral olfactory bulbectomy, sham-operation and inducement of peripheral anosmia were studied on locomotor activity, passive avoidance acquisition and irritability. 2.

A new animal model for the prediction of antidepressant activity.

Animal models presently in use for the screening of potential antidepressant drugs yield numerous false positives and false negatives. In search of a more specific model, we have studied the effects of psychotropic compounds on the behavioural changes induced in rats by the removal of the olfactory bulbs. We have observed that subchronic treatment with antidepressants in general reverses the behavioural alterations displayed by bulbectomized rats in tests of conditioned behaviour.

Changes in muscle action potentials of patients with diseases of motor units following the infusion of a peptide fragment of ACTH.

The polypeptides ACTH and ATCH4-10 (OI 63) witha sequence of amino acids H-Met-Glu-His-Phe-Arg-Trp-Gly-OH, have similar stimulating effects on motor units in lower mammals. Their actions differ primarily in that ACTH4-10 is not corticotropic. Since the corticotropic action of ACTH frequently presents a problem during its clinical use in treatment of motor unit diseases, the action of ACTH4-10 was studied in two patients with muscular atrophy.

Effects of various drugs supposed to interact with serotonin on PGO frequency changes induced by reserpine and 5-hydroxytryptophan.

Reserpine induced ponto-geniculo-occipital (PGO) spikes in the lateral geniculate nucleus. This was used as a model to evaluate the possible anti-reserpine effects of Org GB 94-1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino [1,2-alpha]azepine monohydrochloride-methiothepin, imipramine and atropine. In cats, under local anaesthesia, 3.

Reversal of amnesia by an orally active ACTH 4-9 analog (Org 2766).

The ACTH 4-9 analog, H-Met((O2)-Glu-His-Ph-D-Lys-Phe-OH (Or 2766), attenuates in rats CO2-induced amnesia for a one-trial passive avoidance step-through response when administered prior to the retrieval test but not when given prior to acquisition. Even a dose of 0.001 mug/rat Org 2766 yields an anti-amnesic effect.