Monoamines and sexual function in rats bred for increased catatonic reactivity.

Body weight, ovary and uterus weight, the nature of estral cycles, and hypothalamus dopamine and noradrenaline levels and plasma testosterone levels were studied in female GC rats, bred for increased catatonic reactivity, at different stages of the estral cycle (estrus, proestrus). The outbred Wistar strain served as controls. On the background of decreased body weight, GC females showed impairments to the morphological cyclical changes in the ovaries and uterus, with a reduction in ovary weight in diestrus (p < 0.01) and a smaller estrogen-dependent increase in uterus weight in estrus as compared with Wistar females. On the background of decreases in dopamine and noradrenaline contents in the hypothalamus, GC rats showed higher levels of these monoamines in estrus and lower levels in diestrus. Plasma testosterone levels in female GC rats were higher in diestrus than in estrus and in Wistar rats.

[Monoamines and reproductive function of rats selected for strengthening of catatonia response].

Weights of the body, ovaries, and uterus; estrous cycles and the contents of dopamine (DA) and norepinephrine (NE) in the hypothalami, and testosterone in blood plasma of GC females were studied at various estrous stages (diestrus and estrus). The outbred Wistar line was used as a control. In addition to reduced body weight in GC females, we observed disturbed morphological cyclic linkages between the ovaries and uterus: ovary weight reduction in diestrus (p < 0.01) and lower estrogen-related increase in uterus weight in estrus in GC females in comparison with Wistar ones. While the contents of DA and NE in GC hypothalami were reduced, the levels of these monoamines were high in estrus and low in diestrus. Testosterone levels in GC female plasma in diestrus were higher than in estrus or in Wistar rats.

[Matrix transdermal systems for caffeine delivery based on polymer and emulsion compounds].

The goal of this work was to develop and test transdermal therapeutic systems for caffeine delivery. In vitro experiments showed that the rate of caffeine diffusion through untreated rabbit skin from a transdermal therapeutic systems based on polymer compound containing 50 mg medicine was 67.2 (9.1 microg/cm2h; for a system based on emulsion compound it was 173 (19 microg/cm2h. Methods for studying the caffeine release rate and quantitative measurement of caffeine content in the emulsion-based transdermal therapeutic system were developed. These methods are required to obtain data for standard drug documentation. The results of in vivo experiments in rabbits showed the absence of irritating effect of the emulsion-based transdermal therapeutic system. The obtained data on the specific efficiency of the transdermal therapeutic systems for caffeine delivery (50 mg) in healthy volunteers showed that this medicine could be used as a nonnarcotic psychoactivator for improving mental and physical activities and attention concentration.

Effects of administration of sodium glutamate during the neonatal period on behavior and blood corticosterone levels in male mice.

Treatment of male DBA/2 mice with sodium glutamate (4 mg/g) on postnatal days 1, 3, 5, 7, and 9 induced reductions in the numbers of square crossings, vertical rearings, excursions to the center, and the time spent in the center in adulthood, as compared with a group of males given physiological saline at the same times. These measures showed no change as compared with intact animals. In the light-dark test, the time spent by mice in the light sector was greater after administration of sodium glutamate than after administration of physiological saline but did not differ from that in intact animals. In the acoustic startle reflex test, sodium glutamate decreased startle amplitude but had no effect on the magnitude of prestimulus inhibition. Sexual motivation in males decreased after sodium glutamate, physiological saline producing a tendency to decreased sexual motivation. Neonatal administration of sodium glutamate increased basal blood corticosterone in adult males by a factor of 4, while physiological saline had no effect on this measure. These results lead to the conclusion that neonatal administration of sodium glutamate decreases motor and investigative activity, anxiety, and sexual motivation in adult male mice and increases basal corticosterone. Physiological saline increased all these parameters apart from sexual motivation, though this was not associated with changes in basal corticosterone.

[The effects of neonatal saline injections on behaviours in DBA/2 male mice].

DBA/2 male mice were exposed to the injections of the saline (0.01 ml/g i.p.) on 1-th, 3-th, 5-th, 7-th, 9-th days after birth. Intact males were used as a control group. Adult saline-treated males displayed the increased number of crossed squares, entries in the centre and time spent in the centre during the open "field" test in comparison with intact animals. The time spent in the light compartment of the light-dark box was decreased in saline treated mice compared with intact animals. During the test of acoustic startle response the magnitude of startle reflex and prepulse inhibition didn't change the startle reflex. Saline administration in males did not affect corticosterone basal level. Sexual motivation was revealed to decrease in saline treated males. These data suggest that neonatal administration of saline induced a stable behavioral syndrome in adult DBA/2 male mice: hyperactivity, a decrease of open space fear and simultaneously an increase of some indices of anxiety.

[The effect of neonatal administration of monosodium glutamate on behavior and blood corticosterone level].

DBA/2 male mice were treated with monosodium glutamate (MSG) in a dose of 4 mg/g on 1, 3, 5, 7, 9 days after birth. Saline treated and intact males were used as control groups. MSG treated males displayed decreased number of crossed squares, rearings, entries in the centre and time in the centre of open field in comparison with saline-treated but not intact animals. Time in the light compartment of the light-dark box was increased in MSG-treated mice versus both saline treated and intact animals. MSG administration reduced acoustic startle response but did not affect the magnitude of prepulse inhibition of the startle reflex. Sexual motivation in male mice was reduced by MSG, the same trend was observed after saline treatment. MSG administration increased corticosterone basal level 4-fold while saline treatment did not affect it. These data suggest that neonatal administration of MSG decreases locomotion, exploratory activity, anxiety in male mice, while corticosterone level is increased. Saline treatment increases these parameters (except sexual motivation), and this augmentation is not connected to changes in corticosterone basal level.

[The stress effect in the prenatal period on sexual excitation and sexual orientation of the mice males].

Estrus female behind holed transparent partition produced sexual motivation and sexual arousal in males. It was manifested in behavioral changes (an increase in time spent near the partition) and the testosterone level augmentation in blood. Female mice were exposed to stress (1 h/day restraint) in the last week of gestation. Prenatal stress was shown to decrease the blood corticosterone level as well as to diminish sexual motivation and sexual arousal in adult male mice. Estrus female exposure produced a lesser behavioral response and a lesser testosterone level augmentation. No changes in weight of testicles, seminal vesicles or adrenal glands were found, but preputial gland weight increased. In prenatally stressed males, a female preference decrease and a male preference increase were revealed in the partner preference test. These data suggest that prenatal stress decreases sexual motivation in males and leads to clear predisposition to homosexuality, although it does not produce complete inversion of sexual orientation.

Effect of 5HT2C-receptor agonist MK-212 on blood corticosterone level and behavior in mice.

A dose-dependent the effect of 5HT2C-receptor agonist MK-212 on mouse behavior was demonstrated. Intraperitoneal injection of MK-212 in high doses (0.5 and 1.0 mg/kg) increased blood level of corticosterone in mice and reduced their motor activity. In low doses of 0.1 and 0.2 mg/kg, the agonist reduced anxiety, but had no effect on motor activity. It is hypothesized that low doses of MK-212 exhibited anxiolytic activity in mice.

Effect of 5-HT2C receptor antagonist RS 102221 on mouse behavior.

Injection of RS 102221 (selective antagonist of serotonin 5-HT2C receptors) in a dose of 2 mg/kg reduced anxiety of mice in the light-darkness test and decreased the amplitude of the startle reflex. RS 102221 in a dose of 1 mg/kg reduced prestimulus inhibition of the startle reflex. No behavioral changes in Porsolt test and motor activity in the open field test were detected. Hence, RS 102221 is characterized by selective anxiolytic activity, and 5-HT2C receptors are involved in the mechanisms of anxiety and startle reflex formation.

Effect of neonatal injection of sodium glutamate and diethylnitrosamine on hepatocarcinogenesis, reproductive and adrenocortical systems of male mice.

Neonatal injection of sodium glutamate before injection of diethylnitrosamine decreased the number of tumor nodes in the liver of male mice, decreased the weight of the testes and adrenals and blood level of testosterone (but increased blood level of corticosterone), impaired recovery of diethylnitrosamine-disturbed sexual motivation in half of males. Anticarcinogenic effect of sodium glutamate is explained by feminization of males under its effect.

[Sodium glutamate on some physiological features and chemically induced hepatocarcinogenesis in neontal period in male mice].

A single injection of diethylnitrosamine 50 mg/kg to 12-day old CBA mice led to development of 50.7 +/- 4.8 liver tumor nodules in males and 3.6 +/- 0.8 nodules in females. Only 19.0 +/- 3.6 tumor nodules developed in the liver of males who, prior to the carcinogen, received 5 intraperitoneal injections of monosodium glutamate (2-4 mg/g on alternate days from 1st to 9th days after birth). The glutamate-treated animals' body size diminished, as well as their weights of testes and seminal vesicles and blood testosterone concentration but, as a rule, quantity of body fat increased. The data obtained indicate that neonatal administration of monosodium glutamate to mice leads to disturbance of functional activity of sex steroids and presumably other hormones taking part in regulation of metabolism of body fat and energy.

[Transdermal delivery of insulin]. / Transdermal'nye sistemy vvedeniia insulina.

A possibility is studied of the transdermal delivery of insulin by using a mixture of synthetic analogues of phosphoglycerides (SAP), as a potential activator of hormone diffusion, through the skin. Experimentally in vitro, it was proven that the diffusion of insulin through the skin of two types of transdermal therapeutic form (TTF)--matrix-type and matrix-hydrogel-type--is possible only in presence of activator SAP-M-99. The detected optimal composition of insulin matrix TTF with the area of 40 sq cm enabled a trandermal hormone diffusion speed of 0.26 UNITS/h, which is compatible with the secretion of insulin by the pancreas of an adult (0.25-1.5 UNITS/h). A change-over for the matrix-hydrogel system of insulin delivery based on a 40 sq cm collagenous sponge enabled to increase the insulin diffusion up to 0.54 UNITS/h.