Substance P in the central mechanisms of the escape reaction

The role of substance P in the central mechanisms of escape reaction elicited by electrical stimulation of the ventromedial hypothalamus was investigated in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) led to a short-term (less than 10 min) increase in the threshold of stimulation of the ventromedial hypothalamus and to more stable (up to 1.5 h) disorders of the hippocampal-hypothalamic relations. After substance P injection the inhibitory effects of the dorsal hippocampus but not the facilitating influences of the midbrain reticular formation on excitability of the hypothalamic motivation center were found to be lacking. Disorders of the central mechanisms of escape reaction after substance P injection correlated with new patterns of the main EEG rhythms in different areas of the brain cortex in response to the ascending excitations of the limbic-midbrain structures. Interpreting the mechanisms of substance P involvement in escape reaction the authors point to the ability of the given peptide to interact with different transmitter systems of the brain and opiate receptors and to alter the brain blood circulation.     

Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.     

Limbico-reticular relations during formation of various motivation responses in rabbits subjected to ethanol administration

Chronic experiments on rabbits with electrodes implanted into different limbic-midbrain structures were made to study the effects of a single intravenous injection of ethanol (0.5 g/kg) on the background EEG during formation of food motivation and avoidance behavior from the criterion of the power of the main EEG rhythms. Intravenous injection of ethanol resulted in an increase in the power of beta-, alpha- and theta-rhythms in the frontal cortex, and in that of alpha- and theta-rhythms in the occipital area of the neocortex. New patterns of the powers of the main EEG rhythms recorded in animals exposed to ethanol during electric stimulation of the lateral and ventromedial hypothalamus, evoking food motivation and avoidance behavior, as well as during electrical stimulation of the dorsal hippocamp and mesencephalic reticular formation that correlate with changes in the functions of the study limbic-mesencephalic structures attest to profound ethanol-induced abnormalities of the central mechanisms of food motivation and avoidance behavior.     

Substance P and effects of ethanol on the central mechanisms of the escape reaction in rabbits

Substance P (SP) effects on the central mechanisms of escape reaction, elicited by threshold electrical stimulation of the ventromedial hypothalamus were investigated in rabbits pretreated with ethanol (0.5 g/kg). SP (30 micrograms/kg) was demonstrated to normalize in 71.4% of cases the excitability of the ventromedial hypothalamus which was decreased by ethanol and restored in 83.3% of cases the facilitatory effects of the midbrain reticular formation in escape reactions. However, SP was ineffective in the restoration of the inhibitory effects of the dorsal hippocamp on the excitability of the ventromedial hypothalamus that was obvious in intact animals. Partial normalizing effect of SP on escape reaction in rabbits after previous ethanol administration can be accounted for by the fact that both undecapeptide and ethanol are similar in their realization of central effects such as an interaction with the same brain neurotransmitters, interference with neuronal enzyme processes and reactions with opiate receptors.     

Enhancement of the resistance of the escape reaction to ethanol after substance P]

An ability of substance P (30 micrograms/kg intravenously) to prevent deleterious effects of ethanol (E) (0.5 g/kg intravenously) on central mechanisms of escape reaction elicited by threshold electrical stimulation of the ventromedial hypothalamus was investigated in chronic experiments upon rabbits. Substance P was found to prevent E effects on excitability of the ventromedial hypothalamus (VMH) and on facilitatory influences of the midbrain reticular formation on this emotional centre which were observed in intact animals. Inhibitory effects of the dorsal hippocampus on the VMH could not be evaluated due to its alterations in response to previous substance P administration. The authors suggest that substance P can be considered to be a possible endogenous factor to increase a tolerance of emotional behavioural reactions of an organism to alcohol.     

Responses of neurons of the frontal area of the cortex of the rabbit to electric stimulation of certain limbic-mesencephalic structures after administration of substance P

In rabbits tested on behavioural reactions by electrical stimulation of certain limbic-midbrain structures, intravenous injection of substance P (30 mcg/kg) led after 10 min of silent period to a decrease of spontaneous neuronal activity in the frontal cortex. Convergence of excitations arising from the lateral hypothalamus, the dorsal hippocampus and the midbrain reticular formation was also found to decrease after the substance P injection. Analysis of neuronal responses allowed to establish that substance P markedly changed the ascending excitations of the lateral hypothalamus and was less effective for the influences from the midbrain reticular formation.     

Gastrin in the mechanisms of genetic determination of feeding behavior in rabbits

Spreading of a dominant motivation to the molecular intracellular mechanisms of genetic memory was studied. Blockage of protein synthesis in the nervous system selectively abolishes food motivation in rabbits during stimulation of the lateral hypothalamus but exerts no noticeable effect on avoidance responses during stimulation of the ventromedial hypothalamus. During protein synthesis blockage, food motivation returns to normal upon pentagastrin intracerebroventricular (i.c.v.) injection. Intracerebroventricular administration of antigastrin immunoglobulin inhibits feeding reaction to lateral hypothalamic stimulation but not avoidance response to ventromedial hypothalamic stimulation. It was concluded that feeding motivation translates into feeding behavior in the following stages: motivational excitation, gene activation, mRNA synthesis, formation of a gastrin-like peptide, and expression of feeding behavior.     

Neuroendocrine mechanisms of participation of the raphe nuclei in the development of hypertensive reactions in emotional stress

The experiments on cats and rabbits have studied electroencephalographic, endocrine and blood pressure responses to stress (5-hour immobilization with electrical foot shock) before and after coagulation of the midbrain nuclei raphe. Blood pressure and adrenal responses in advanced (4-hour) stress were elevated in intact animals, the responses attenuating after coagulation of the nuclei raphe. Background bioelectrical activity of the midbrain reticular formation and hypothalamus was found to be activated in the operated animals. Stress was followed by the reduction in bioelectrical changes of the above subcortical structures with the parallel development of "burst" activity in the dorsal hippocamp.     

Characteristics of heterochromatin of heterophase nuclei from interphase neurons of various brain structures selected for the nervous system excitability

Quantitative characteristics (the area and number of chromocenters) of the interphase C-heterochromatin in the nuclei of pyramidal neurons of the midbrain reticular formation, sensorimotor cortex, and hippocampus (CA3) of rat strains with different genetically determined excitability were studied in the normal state of the animals and after exposure to a short-term emotional pain stress. The results indicate a relationship between the excitability of the nervous system and structural-functional state of the neuronal interphase heterochromatin. The role of cytogenetic features of different brain structures in the CNS functioning and behavior and their relation with genetically determined excitability of the nervous system are discussed.     

Influence of lithium hydroxybutyrate on the electroencephalographic effects of fenamin

Lithium hydroxybutyrate (10 mg/kg) prevents the amphetamine-induced EEG arousal and amplitude frequency alterations in the motor and visual cortex, posterior hypothalamus, midbrain reticular formation, and caudate nucleus but potentiates the action of the psychostimulant on the EEG of the hippocamp and amygdala. The response to the light flickering rhythm in the visual cortex remains within initial upon concurrent administration of both the drugs.     

Role of substance P in regulating the feeding behavior and the avoidance reaction in the rabbit

Similar changes in feeding and avoidance reaction in spite of the way of substance P administration (30 mgk/kg intravenously or 14,8 nmol intraventricular) were found in rabbits with electrodes implanted in various limbic-midbrain structures. Feeding was found to be more sensitive to substance P administration, as it was shown by the decrease of excitability of the hypothalamic "feeding center" and abolishing of the inhibitory and facilitatory effects on this center from the dorsal hippocampus and the midbrain reticular formation, correspondingly. New cortical-subcortical integration under substance P was presented in new characteristics of EEG activity in neocortical areas, both background and in response to stimulation of various limbic-midbrain structures. Biochemical data let to suggest that at the neural level substance P led to destabilization of membrane structures in endoplasmatic reticulum and to redistribution of membrane-connected N-acetylneuramine acid which was directly involved in neurotransmission.     

Effect of ethanol on central mechanisms of alimentary and defensive motivation in the rabbit

A single intravenous administration of ethanol (0.5 g/kg) to rabbits had different effects on the excitability of feeding and defensive motivational centers of the lateral and ventromedial hypothalamus. Ethanol abolished both inhibitory effects of the dorsal hippocampus and facilitatory action of the midbrain reticular formation on alimentary and defensive motivations. It elicited new power distributions of the main rhythms of general electrical cortical activity in the background and under stimulation of limbic-midbrain structures. Analysis of the activity of organello-specific enzymes in limbic-midbrain neurones revealed disturbances of cellular energetic processes caused by ethanol.     

The effect of adrenoblockers on the neurons of the lateral hypothalamus under the action of pentagastrin]

To test the hypothesis of interaction pentagastrin (PG) noradrenaline (NA) in central neurochemical mechanisms of food motivation, we studied the activity of single neurons in lateral hypothalamus (LH) after s.c. PG injection. Following PG injection microiontophoresis (MIF) of propranolol prazosin was made. PG-induced changes were similar to neuronal activity in rabbits LH after 24-hour food deprivation in 59%. Propranolol-induced changes were following firing pattern in the process of food uptake in 68%. Prazosin MIF induced firing pattern of neuronal activity of saturated rabbits in 60%.     

Effect of stimulation of the reticular formation on the motivational and reinforcing effects of the self stimulation zones

The influence was studied on the midbrain reticular formation (RF) on motivational and reinforcing effects of stimulation of the same selfstimulation zones (SS) of hypothalamic area. A current of gradually increasing intensity was used, by means of which three groups of functionally (behaviourally) specific reticular points were revealed: motivationaly neutral, positive and negative. The data obtained show that influences of RF on SS zones of hypothalamus differand depend on functional properties of various RF areas. Changes of motivational effects in SS zones reflex the specificity of reticular foci in a lesser degree than changes in reinforcing effects. It has been suggested that reinforcing effects of the SS hypothalamic zones possess their own activating mechanism specifically related to its "positive" link and differing from reticular mechanism of unspecific activation.     

Effect of substance P on catecholamine levels in the hypothalamus and midbrain in the rat during immobilization stress

Single intraperitoneal injection of substance P in a dose of 125 mcg/kg induced a significant increase of noradrenaline and dopamine level in the hypothalamus and the midbrain of intact rats. Under conditions of immobilization emotional stress, the substance P eliminated the stress induced decrease of hypothalamic noradrenaline and increase of its level in the midbrain; in other words the substance P normalized the noradrenaline level. Modulatory effect of a single injection of the substance P had a long-term character and was synchronized with an earlier found increase of resistability of rats to chronic emotional stress.     

An analysis of the neuronal processes in the activating brain systems of the rat during the acquisition of an instrumental defense reflex

In chronic experiment, a defensive conditioned reflex was elaborated in rats with electrodes implanted in the reticular oral pons nucleus, cortico-medial group of amygdalar nuclei, ventromedial hypothalamic nucleus and central grey substance of the midbrain. Synchronization of the activity of neuronal groups of emotiogenic formations in the studied brain structures, became enhanced at formation of the conditioned reflex. A dependence was revealed of the level of correlation of limbic neuronal groups activity on functional state of the reticular formation, as well as neurochemical correlation mechanisms. The increase (decrease) of coefficients of correlation of the activity of neuronal ensembles of limbic structures was accompanied by a change of evoked potentials parameters recorded in them.     

Characteristics of memory and the functional organization of the hippocampo-reticulo-neocortical complex of the brain in the acute postoperative period

In tests on dogs, rabbits and rats, it has been established that in acute postoperative period, the time of memorizing of conditioned signals (light, tone and metronome) is reduced, the time of realization of conditioned reactions increases, the excitability and the bloodflow of the midbrain reticular formation and Mg-AtPhase activity of pons Varolii raise. In the hippocampus the excitability and local bloodflow lower and the activity of Ca-Mg-ATPhase is enhanced. In the frontal cortex these processes do not change. Functional interrelations of the brain structures in the acute postoperative period are characterized by the weakening of the activating influence of the reticular formation on the frontal cortex and an increase of its suppressive action on the dorsal hippocampus. It is suggested, that the discovered damages in the higher nervous activity are stipulated by the changes in neurochemical organization of the brain.     

Participation of the posterior hypothalamus in the activity of the ascending activating system]

In chronic experiments on cats with premezencaphalic section of the brain stem electrica stimulation of the posterior hypothalamus caused desynchronization of the electrical activity of the neocortex. After the isolated injury of the posterior hypothalamus a moderate electrical stimulation of the medical part of the midbrain reticular formation failed to cause any pronounced activation of the neocortex. The results obtained indicated an important role of the posterior hypothalamus in the function of the ascending activating system.     

Spectral analysis of the effects of nomifensine on bioelectric activity of the rat brain]

The influence of nomifensine on bioelectrical activity of sensorimotor cortex, dorsal hippocamp and lateral hypothalamus in conscious rats in free behavior was studied. The pharmacological and EEG analysis of nomifensine action on EEG power spectra by Fourier technique was measured. It was established that nomifensine evoked an increase and stabilization of the dominant peak in EEG spectra in the left and right cortex and in the left hippocamp, while in the other ranges of frequency a decrease was observed. The effects on hypothalamus was opposite--EEG power spectra decreased in all the ranges. The authors conclude that nomifensine evokes higher level of wakefulness, vigilance of the animals. This is likely to underlie neurophysiological mechanisms of optimal behavior due to stimulants of CNS, including nomifensine.     

Central nervous system actions of growth hormone on brain monoamine levels and behavior of juvenile rainbow trout

Growth hormone (GH) has been demonstrated to alter the behavior of juvenile salmonids. However, the mechanisms behind this action are not yet understood. In mammals and birds, peripheral GH treatment has been shown to affect monoaminergic activity in the central nervous system, which may be a mechanism whereby GH alters behavior. To investigate if GH may influence behavior directly at the central nervous system, juvenile rainbow trout were injected with GH into the third ventricle of the brain, whereupon physical activity and food intake were observed during 2 h. Thereafter, brains were sampled and the content of serotonin, dopamine, and noradrenaline and their metabolites were measured in hypothalamus, telencephalon, optic tectum, and brainstem. The GH-treated fish increased their swimming activity relative to sham-injected controls, while appetite remained unchanged, compared with sham-injected controls. Analysis of brain content of monoamines revealed that the GH treatment caused a decrease in the dopamine metabolite homovanillic acid in the hypothalamus, indicating a lowered dopaminergic activity. It is concluded that GH may alter behavior by acting directly on the central nervous system in juvenile rainbow trout. Furthermore, GH seems to alter the dopaminergic activity in the hypothalamus. Whether this is a mechanism whereby GH affects swimming activity remains to be clarified.