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.     

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.     

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.     

Substance P in the central mechanism of the rabbit feeding response evoked by stimulation of the lateral hypothalamus

The effects of substance P on the central mechanisms of food motivation elicited by electrical stimulation of the lateral hypothalamus were studied in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) brought about a dramatic reduction in the excitability of the "food center" in the hypothalamus, which returned to normal 45-60 minutes after injection. Higher concentrations of substance P provoked food behavior inversion up to the replacement of food motivation by avoidance behavior. Intravenous injections of substance P disturbed the relationships between the hippocamp, midbrain reticular formation and hypothalamus seen in health. This manifested in complete cessation of the inhibitory effects of the dorsal hippocamp and facilitating influences of the midbrain reticular formation on the excitability of the hypothalamic "food center". It is assumed that disorders of the central mechanisms of food motivation may arise from the effects produced by substance P directly on the central nervous system or on the brain via changes in the hormonal balance and responses of the autonomous nervous system.     

Influence of renin on the effects of electric stimulation on the ventromedial hypothalamus

The influence of intraventricular injection of different doses of renin on the effects of electrical stimulation of the ventromedial hypothalamus was studied. Injection of renin (10 micrograms/kg) into the lateral ventricles of the brain of experimental animals elicited a prolonged elevation of arterial pressure and a decrease of the heart rate, while given in doses of 20 and 30 micrograms/kg it also provoked arrhythmias and ventricular extrasystoles, and a lowering of the threshold of ventromedial hypothalamus stimulation. It was found that under the central action of renin, a short-term stimulation of the ventromedial hypothalamus provoked ventricular extrasystoles.     

Vasoactive peptides in the structure of defensive motivational excitation

In experiments on rabbits, the action was studied of vasoactive peptides angiotensin-II, bradykinin and lysyl-vasopressin, injected into the brain ventricles, on a passive defensive reaction to electrical stimulation of the ventromedial hypothalamus. It was found that angiotensin-II and lysyl-vasopressin had a pronounced inhibitory influence, while bradykinin had a facilitatory effect on this reaction. Electrical stimulation of the ventromedial hypothalamus predominantly facilitated reactions of individual neurones of the sensorimotor cortex to angiotensin-II and bradykinin. Intraperitoneal injection of P-substance to rats in conditions of an acute conflict situation producing an emotional stress, brought about a significant diminution of sudden death incidence from cardiovascular insufficiency.     

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.     

Central and peripheral proglumide administration and cholecystokinin-induced satiety

Peripheral (50 mg/ml) or central (50 micrograms/microliter) injections of proglumide were made into Sprague-Dawley rats which displayed satiety-like responses after the peripheral (100 micrograms/kg) or central (50 ng in 1 microliter) administration of cholecystokinin (CCK). The satiety produced by CCK injection into the lateral hypothalamus, area postraema and ventromedial hypothalamus was significantly reversed by proglumide injections into these areas during a 4 h food intake test. Peripheral injection of proglumide after central or peripheral CCK injection did not modify this type of CCK-induced satiety. Central proglumide injection produced a reliable decrease in water intake and this is compatible with previous findings which describe the stimulation of water intake after central gastrin administration. These results suggest that various central and peripheral mechanisms which are involved in the regulation of appetite may function independently as a 'failsafe' system.     

Beta-adrenoblockers in the reorganizing of the food center of the hypothalamus under the influence of substance P]

An ability of substance P (15 nmol intracerebroventricularly) to transform functional properties of the hypothalamic feeding center manifested in escape reaction in response to threshold electrical stimulation of this motivation center in rabbits. Beta-adrenergic antagonists inderal and obsidan (0.25, 0.5 mg, respectively) injected intravenously were found to restore feeding elicited by electrostimulation of the hypothalamic feeding center. However, escape reaction, elicited from the feeding center under substance P was found unchanged after intravenous administration of 0.25 mg kalipsol. The data obtained suggested an important role of beta-adrenergic mechanisms in substance P transformation of the functional properties of the hypothalamic feeding centre.     

Role of the hypothalamus in inhibiting the hypophysis-adrenal cortex system through the feedback mechanism

Chronic experiments were made on intact rabbits and rabbits with destroyed paraventricular and ventromedial nuclei of the hypothalamus to explore the hydrocortisone-induced inhibition of the stressor response of the pituitary-adrenocortical system. Intravenous injection of hydrocortisone in a dose of 100 micrograms/kg 5 minutes before immobilization stress led to inhibition of corticosteroid elevation induced by immobilization of the animals. Inhibition of the stressor reaction was maximal in intact animals, less in rabbits with destroyed ventromedial nuclei, and further less in animals with destroyed paraventricular nuclei. The paraventricular and ventromedial nuclei of the hypothalamus are necessary for inhibition of the pituitary-adrenocortical system by the feedback mechanisms.     

The central efferent mechanism of brown adipose tissue thermogenesis induced by preoptic cooling

This study was performed to investigate central efferent mechanisms for brown adipose tissue thermogenesis. In unanesthetized rats, the effects of local anesthesia of the ventromedial hypothalamus, anterior hypothalamus, and lateral hypothalamus were observed on the brown adipose tissue thermogenesis induced by preoptic cooling. Rats had a thermode, thermocouple, and bilateral injection cannulae chronically implanted in the hypothalamus and a thermocouple beneath the interscapular brown adipose tissue. The experiments were done at an ambient temperature of 24-25 degrees C. Preoptic cooling increased brown adipose tissue and colonic temperatures without shivering. Injecting lidocaine bilaterally into the ventromedial hypothalamus during preoptic cooling reduced brown adipose tissue temperature (Tbat). The mean maximum decrease of Tbat was 0.51 +/- 0.26 degrees C and occurred 5-8 min after lidocaine injection. When lidocaine was injected into the anterior hypothalamus, Tbat increased. The mean maximum increase of Tbat was 0.85 +/- 0.29 degrees C and occurred 4-9 min after lidocaine injection. In the lateral hypothalamus, lidocaine had no effect on Tbat. Tbat was not influenced by injection of saline into the ventromedial, anterior, or lateral hypothalamus. The efferent pathway from preoptic to brown adipose tissue may thus traverse the medial part of hypothalamus. The ventromedial hypothalamus facilitates and anterior hypothalamus inhibits brown adipose tissue thermogenesis induced by preoptic cooling.     

Changes in the substance P content of the blood and hypothalamus during experimental emotional stress

A study was made of the content of substance P in the blood and hypothalamus of Wistar rat brain in acute and chronic emotional stress and after intraperitoneal injection of substance P in a dose of 250 mg/kg. A possibility was demonstrated of inducing long-term changes in the content of substance P in the hypothalamus after a single injection. Exposure to a single 24-hour stress was followed by an increase in the substance P content in the hypothalamus.     

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.     

Role of angiotensin II in elaborating the escape reaction during electric stimulation of the ventromedial hypothalamus in rabbits

The action of angiotensin-II, saralazin, captopril and antiserum to angiotensin-II, injected into the brain ventricles, on avoidance reaction to electrical stimulation of ventromedial hypothalamus was studied in experiments on rabbits. It has been found that angiotensin-II had a pronounced inhibitory effect, while saralazin, captopril and antiserum to angiotensin-II had a facilitating effect on the reaction.     

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.     

A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats

Progesterone (P) facilitation of sexual receptivity in rodents has been achieved by intracranial administration to the ventral hypothalamus; the preoptic area; and midbrain areas such as central gray, mesencephalic reticular formation, and ventral tegmental nucleus. In our laboratory, by far the most effective site in rats has been the ventromedial nucleus of the hypothalamus (VMN). However, several reports of sensitivity to P in the midbrain of rats and other rodent species led us to investigate whether stimulation of the ventral midbrain of female rats might contribute to facilitation of sexual receptivity. Ovariectomized Long-Evans rats received one cannula aimed at the VMN, and another aimed at the contralateral ventral mesencephalon. P in both cannulae, following a priming dose of estradiol, caused significantly higher lordosis quotients (LQ) than blank tubes. Controls with bilateral cannulae in the VMN responded when both tubes were filled with P, but did not respond to unilateral VMN P stimulation. P in the VMN and contralateral anterior preoptic area did not result in a greater degree of receptivity than did the empty tubes. These studies indicate that although progesterone stimulation in the midbrain alone is not sufficient to facilitate receptivity in female rats with our methods, the midbrain may play an auxiliary role. P implants in the midbrain appear to facilitate receptivity in the case of VMN implant treatments that are subthreshold for stimulating lordosis. The results are discussed in light of similar studies in other rodent species, and in the context that more than one brain site may be important in the natural stimulation of sexual receptivity by gonadal hormones.     

Relation between the dynamics of a species-specific motor reaction and the duration of diencephalic stimulation

Species-specific reaction of thumping behaviour with the hind limbs in response to electrical stimulation of the ventromedial, dorsomedial and caudal parts of the hypothalamus was studied in chronic experiments on rabbits. Reaction of avoidance dominated during current action of various durations (1-20 s). The specific reaction under study appeared after the termination of stimulation and lasted for 30-120 s. The number of kicks in response to single stimulation depended on its duration (T). With T rising from 1 to 10 s, the number of kicks increased; with T being equal to 20 s, it decreased. The latency of the first kick after the termination of stimulation regularily increased with increase of its duration, and reaction intensity maxima shifted to the right along the axis of time. Possible mechanisms of limb kicking behaviour are discussed based on a transition of avoidance reaction during stimulus action to emotional reaction in post-stimulus period.     

刺激兔下丘脑室旁核诱发的心律失常与增压反应

在60只局麻与肌松剂制动的家兔,观察到用0.1—0.4mA,50Hz,1ms 的方波电刺激下丘脑室旁核(PV)能诱发频发性心律失常(包括室性与室上性期前收缩)及显著的动脉血压升高。与同侧的下丘脑外侧区(LHA)及腹内侧核(VMH)相比,刺激PV诱发期前收缩的次数更为频繁,增压反应幅度较大,且所需阈值亦较低。较低强度刺激LHA 在部分兔能引起血压下降与心率减慢,而PV 则一致地诱发增压反应。电刺激腓深神经能抑制刺激PV诱发的期前收缩,但在中脑中央灰质微量注射吗啡或电解毁损只能完全阻断刺激VMH诱发的期前收缩,而不能完全阻断PV诱发的期前收缩。这些结果提示,PV是下丘脑中诱发心律失常与血压增高的高反应区之一,并且可能具有不同于LHA或VMH的神经机制或下行神经通路。     

Progestin receptors in substance P-immunoreactive neurons in the hypothalamus of male guinea pigs after behaviorally effective estradiol pulse treatment

Pulsatile administration of estradiol effectively primes orchidectomized (ORCH) male guinea pigs to display progesterone-facilitated lordosis. In contrast, a single injection of estradiol benzoate (EB) is not behaviorally effective. In ovariectomized female guinea pigs, estradiol pulses induce progestin receptors selectively in substance P neurons in the ventrolateral hypothalamus (VLH), a site at which estradiol primes females to respond behaviorally to progesterone. To test the hypothesis that behaviorally effective estradiol pulses induce progestin receptors selectively in substance P neurons in the VLH in males, ORCH animals received a single injection of EB 40 h before, or two pulses of estradiol-17β, 39 and 11 h before perfusion. Colchicine was administered intracerebroventricularly prior to perfusion. The only difference found between the two estradiol treatment groups was a higher number of progestin receptorimmunoreactive (PR-IR) cells in the rostral VLH of estradiol pulse-treated males. There were no significant differences in the number of PR-IR cells in the mid- or caudal VLH, nor in the number of substance P-immunoreactive (SP-IR) neurons in the VLH/ventromedial hypothalamus (VMH) of animals receiving the two estradiol treatments. Furthermore, the percentage of PR-IR cells in the VLH also immunoreactive for SP did not differ between the estradiol pulse- (22%–25%) and the EB-injected animals (22%–32%). These data do not support the hypothesis that administration of behaviorally effective estradiol pulses, as compared to behaviorally ineffective EB injections, induce progestin receptors selectively in substance P neurons in the VLH of male guinea pigs.     

Progestin receptors in substance P-immunoreactive neurons in the hypothalamus of male guinea pigs after behaviorally effective estradiol pulse treatment.

Pulsatile administration of estradiol effectively primes orchidectomized (ORCH) male guinea pigs to display progesterone-facilitated lordosis. In contrast, a single injection of estradiol benzoate (EB) is not behaviorally effective. In ovariectomized female guinea pigs, estradiol pulses induce progestin receptors selectively in substance P neurons in the ventrolateral hypothalamus (VLH), a site at which estradiol primes females to respond behaviorally to progesterone. To test the hypothesis that behaviorally effective estradiol pulses induce progestin receptors selectively in substance P neurons in the VLH in males, ORCH animals received a single injection of EB 40 h before, or two pulses of estradiol-17 beta, 39 and 11 h before perfusion. Colchicine was administered intracerebroventricularly prior to perfusion. The only difference found between the two estradiol treatment groups was a higher number of progestin receptor-immunoreactive (PR-IR) cells in the rostral VLH of estradiol pulse-treated males. There were no significant differences in the number of PR-IR cells in the mid- or caudal VLH, nor in the number of substance P-immunoreactive (SP-IR) neurons in the VLH/ventromedial hypothalamus (VMH) of animals receiving the two estradiol treatments. Furthermore, the percentage of PR-IR cells in the VLH also immunoreactive for SP did not differ between the estradiol pulse- (22%-25%) and the EB-injected animals (22%-32%). These data do not support the hypothesis that administration of behaviorally effective estradiol pulses, as compared to behaviorally ineffective EB injections, induce progestin receptors selectively in substance P neurons in the VLH of male guinea pigs.