Milan Rezek

Somatostatin and thyrotropin releasing hormone: Central effect on sleep and motor system☆

The hypothalamic hormones, somatostatin (SRIF or GH-RIH) and thyrotropin releasing hormone (TRH) applied intraventricularly into rat brain had a considerable effect on motor function and resulted in profound alterations in the sleep-waking pattern. While TRH induced primarily an increase in exploratory and motor stereotyped behavior, the effect of somatostatin was striking and prolonged: stereotyped circular running in many instances evolved into catatonia, paraplegia-in extension and/or tonic-clonic seizures.

Behavioural and motor excitation and inhibition induced by the administration of small and large doses of somatostatin into the amygdala.

Abstract The administration of lower (0.01, 0.1 μg) and higher (1.0, 10.0 μg) doses of somatostatin (SRIF) into the amygdaloid complex revealed a dose-dependent dissociation of effects on behaviour and motor control. While the lower doses generally induced a behavioural excitation accompanied by a variety of tremors and stereotyped movements, the higher doses prevented the expression of a normal behavioural pattern due to the severity of disturbances in motor control. The sleep-waking cycle was also affected; the duration of REM sleep showed a consistent dose-related reduction although the total sleeping time was not considerably altered. This was due to a paradoxical dose-related prolongation of shallow slow wave sleep (drowsiness) which typically accompanied the periods of immobilization caused by motor control difficulties. Electrophysiologically, this phenomenon was often reflected in a paradoxical pattern characterized by a dissociation of EEG from behaviour. The specificity of SRIF effects was tested by administration of some endocrinologically active and inactive analogues of SRIF via the same route. None of the analogues tested induced effects comparable to those observed after the administration of the same dose of the native hormone.

Cortical administration of somatostatin (SRIF): Effect on sleep and motor behavior☆

Cortical administration of SRIF in unrestrained, freely moving rats produced an early activation, stereotyped behavior patterns and later, coordination difficulties often associated with drowsiness. A few animals showed a tendency toward paraplegia-in-extension. A considerable, prolonged alteration in the sleep-waking cycle was also observed. Similar results were obtained in both intact and hypophysectomized animals. Intraperitoneal administration of SRIF induced several other effects in addition to those seen after cortical application. The latter were however, restricted in variety, intensity and duration.

Central site of action of somatostatin (SRIF): role of hippocampus.

Abstract The direct cerebral administration of somatotropin release inhibiting factor (SRIF) into two loci of the hippocampal formation induced a variety of behavioural, motor and electrophysiological changes. These were characterized by several patterns of stereotyped behaviour, alteration of the sleepwaking cycle and frequent dissociation of the EEG from behaviour. Both behavioural and electrophysiological phenomena were found to be dose-related. The administration of SRIF analogues via the same route failed to produce comparable effects, thus suggesting the specificity of SRIF action within the central nervous system. The results indicate that the hippocampus is involved in mediating the central, nonendocrine action of SRIF and are consistent with the hypothesis proposing the existence of a limbic pacemaker controlling stereotyped behaviour.

Paradoxical stimulation of food intake by larger loads of glucose, fructose and mannose: Evidence for a positive feedback effect☆

Abstract The phenomenon of paradoxical stimulation of food intake by larger alimentary loads of isotonic glucose was studied with regard to a variety of experimental and nutritional conditions. Thus, paradoxical feeding response was induced not only by the infusions of glucose but also of the other insulinogenic sugars—fructose and mannose. Stimulation of food intake was further observed following the administration of larger volumes of isotonic glucose solutions via the duodenal and intraperitoneal infusion routes in free feeding as well as in 12 hr food-deprived animals. This paradoxical alimentary response was not eliminated or reduced by repeating these infusions daily over a longer period of time; in fact, food in the first postinfusions hour and, unexpectedly, also the total daily food intakes, showed a gradually increasing trend with daily repetitions. Drinking of isotonic glucose for 1 hr in 12 hr water-deprived animals did not suppress the subsequent intake of regular food despite the substantial amount of glucose drunk (94.1 ml vs 76.5 ml of water in controls during the same time period). The conbination of glucose drinking with subsequent food intake resulted in a significant caloric imbalance during the first hour which was not fully compensated within the 24 hr. These findings indicate that larger loads of insulinogenic sugar loads are capable of triggering an antiregulatory positive feedback alimentary response which can induce caloric imbalance and thus adversely affects the short-term maintenance of energy balance.

Caloric imbalance induced by failure of food intake to compensate for caloric supply provided by diurnal or nocturnal drinking of isotonic glucose

Abstract Free-feeding rabbits allowed to drink isotonic glucose failed to reduce food intake sufficiently to compensate for the extra caloric supply. This resulted in a considerable caloric imbalance which was not compensated during the diurnal or nocturnal periods when the animals were drinking glucose. Reductions of food intake were smaller or even paradoxically reversed following repeated exposures to glucose despite the fact that the intake of fluids was more doubled. Equi-osmotic equi-volumic saccharin solutions drank voluntarily or infused into the duodenum did not produce paradoxical feeding response. Blockade of insulin-dependent lipogenesis by Atromid S prevented the paradoxical stimulation of food intake by larger duodenal loads of glucose.

A chronic intracerebral cannula

The preparation of a chronic intracerebral cannula from disposable regular and dental needles is described. The cannula system has a convenient and reliable locking arrangement between the exteriorized part of the implanted cannula guide and a terminal plug of the extension tube. This arrangement enables to perform the infusions of experimental substances by a remote control in unrestrained, freely moving animals. Between infusions, the cannula guide is protected by a removable cap with fixed cleaning wire to prevent the infection and clogging.

Cannula for intracerebral administration of experimental substances

Two reliable intracerebral cannulas, with a protective cap and a locking arrangement of the extension tube can be made from inexpensive regular and dental disposable needles and syringes. The preparation and use of these alternative cannula systems which enable the prolonged intracerebral infusion of experimental substances in unrestrained, freely moving animals is described.

Chronic multipurpose cannulas and a technique for the cannulation of small veins and arteries

Simple, inexpensive, and reliable cannula systems for the infusion of experimental substances in chronic, unrestrained animals are described. A cannula with a removable cap is convenient for infusions of experimental substances and nutrients into various parts of the digestive tract. Intravenous infusions can be performed through a closed system cannula which avoids a possible introduction of air into the circulation. With the use of both cannula systems, blood samples and samples of the digestive tract content can be taken. To facilitate the cannulation of small veins and arteries, a simple device was developed. Its preparation and use is also described.

Cerebroventricular administration of somatostatin (SRIF): Effect on central levels of cyclic AMP

Abstract The changes in cAMP levels in the hippocampus, cerebral cortex and the neostriatum were investigated at different times after the cerebroventricular administration of SRIF. An early significant increase in cAMP levels (at 5 minutes) in the hippocampus induced by SRIF was eliminated by pretreatment with sotalol. However, the overall behavioral response to SRIF was not affected by sotalol. Sotalol itself significantly reduced cAMP levels in control experiments. In cerebral cortex, an SRIF-induced increase in cAMP levels was significantly lowered by sotalol pretreatment at both 5 and 15 minutes post-SRIF. In neostriatum, a sustained elevation in cAMP levels was observed at 5 and 15 minutes after the intraventricular infusion of SRIF. Sotalol pretreatment failed to reduce the cAMP levels although it lowered its increase at 15 min. post-SRIF. The results appear to show a beta adrenergic involvement in the cAMP response to SRIF and an apparent independence of the behavioral response from cAMP changes.