Tonic pain response during inflammation and stress-induced corticosterone variations in prenatally stressed infant rats: effects of maternal buspirone injected during pregnancy.

We studied the effects of injections of 5-HT1A-agonist buspirone to pregnant rats before stress exposure on corticosterone level in the dynamics of stress response to inflammatory-induced pain in 7-day-old offspring. During the period of the hypothalamic-pituitary-adrenal system hyporeactivity, the pain response in the formalin test was associated with stress-related corticosterone variations. Maternal buspirone normalized the pain reaction in prenatally stressed rats during all periods of the formalin test and modified the dynamics of the corticosterone response. In 1 day after the formalin test, the basal level of this hormone in blood plasma remained increased. Maternal buspirone increased the resistance of the nociceptive and stress-systems to inflammatory-induced pain response in prenatally stressed rats.

Early and delayed effects of hypoxia during the infantile period on behavioral and hormonal reactions of rats.

We studied the early and delayed effects of hypoxia during the infantile period on the behavioral reactions and corticosterone concentration in male rats. The elevation of corticosterone concentration, decrease in the immobility time (forced swimming test), and increase in the nociceptive response (formalin test) were observed in 7-day-old rats immediately after hypoxia. Adult animals exposed to hypoxia at the age of 7 days exhibited elevated basal corticosterone level and lengthened immobility time. Hypoxia had the same effect on plasma corticosterone concentration in 7-day-old and adult rats. Changes in corticosterone concentration after forced swimming were shown to differ in hypoxic animals and non-hypoxic specimens. Studying the dynamics of age-related variations in the test parameters will contribute to the understanding of pathogenetic mechanisms and development of new methods for pharmacological correction of postnatal changes in CNS after hypoxia during early ontogeny.

Persistent pain responses in inflammation and corticosterone levels in juvenile rats born to adrenalectomized dams.

Studies in juvenile (Wistar) rats born to adrenalectomized dams (surgery performed 3-4 weeks before mating) addressed the intensity of behavioral pain responses (numbers of flexion + shaking patterns and durations of licking patterns) induced by foci of inflammation in the formalin test and plasma corticosterone levels on the background of the pain response. Maternal adrenalectomy had no effect on basal corticosterone levels or measures of the intensity of the pain response. In conditions of persistent pain (25 min after injection of formalin), corticosterone levels significantly (p < 0.05) increased in the offspring of both intact and operated dams. Females born to adrenalectomized dams, as compared with females from shamoperated dams, showed higher (p = 0.008) hormone levels in response to persistent pain. There were no differences in measures of the pain responses of the female offspring of adrenalectomized and sham-operated dams. There were no gender differences in measures of the pain response and hormone levels. Thus, pain evoked by acute foci of inflammation in the formalin test activated the hypothalamo-hypophysealadrenal system in 25-day-old rats, though the corticosterone released did not decrease pain intensity, which is consistent with data obtained from the offspring of adrenalectomized dams.

[Persistent pain responses under inflammation and corticosterone levels in juvenile rats born to adrenalectomized dams].

Juvenile Wistar rats born to dams adrenalectomized 34 weeks before mating were used to study the intensity of indices of behavioural pain responses (number of flexing + shaking and duration of licking patterns) produced by inflammation in the formation test as well as plasma corticosterone levels during the pain response. It has been found that dams' adrenalectomy does not change either basal corticosterone levels or the indices of pain response intensity. During persistent pain (25 min after the formation injection), corticosterone levels were enhanced reliably (p < 0.05) in offspring of both intact and adrenalectomized dams. Females born to adrenalectomized dams showed the higher corticosterone levels (p = 0.008) as a response to persistent pain as compared to those born to sham-operated dams. No differences in pain indices in female offspring of adrenalectomized and sham dams were revealed. There were no sex differences in the indices of pain response and corticosterone. Thus, the pain evoked by inflammation in the formalin test has an activating effect on the hypothalamo-hypophyseal-adrenocortical system in 25-day-old pups, but the released corticosterone fails to reduce pain intensity in the formalin test as evidenced by data obtained in offspring of adrenalectomized dams.

[Behavior of female and male mice submitted to action of p-chlorophenylalanine in prenatal ontogenesis].

Effect of serotonin (5-HT) deficit produced by administration ofp-chlorophenylalanine at a dose of 400 mg/kg to pregnant female mice on the day 8 of gestation and on the subsequent behavior of their offspring (hybrids F1 (C57BL/CBA)) was studied. The 5-HT deficit in prenatal ontogenesis leads to the following changes of behavior: 1) females and males of the experimental group show a higher level of the explorative activity in the "open field" than control animals; 2) in females of the experimental group at the age of 90 days, unlike control females and males of experimental and control groups, the explorative activity is extinguished at the threefold testing in the "open field"; 3) females of the experimental group have a decreased level of anxiety in tests "elevated plus-maze" and the "dark-light chamber". Males of the experimental group, on the contrary, have an elevated level of anxiety. The obtained data show that the 5-HT deficit at the prenatal period affects various aspects of behavior. The degree of the changes produced by the prenatal 5-HT deficit can have different manifestation depending on sex of the animals.

[Antinociceptive properties of the 5-HT3 receptor antagonist in the model of inflammatory pain in rats of different age with prenatal deficit of serotonine and under stress].

The role of peripheral 5-HT3 receptors in the nociceptive behavioral response and the effect of the 5-HT3 antagonist ondansetron on indices of acute and tonic pain were investigated in the formalin test in 25- and 90-day-old Wistar male rats. The experimental rats were prenatally exposed to 5-HT depletion (a single injection ofparachlorophenilalanine 400 mg/kg/2 ml, i. p.; ICN, USA to the dams on day 9 of pregnancy) and to stress (dams immobilization during the last week of pregnancy). Antinociceptive effects of ondansetron in the rats with both prenatal 5-HT deficiency and stress (experimental rats) and prenatal injection of saline solution and stress (control rats) were more obvious in the younger animals. Prenatal 5-HT deficiency attenuated the antinociceptive effect of ondansetron in licking patterns in the younder age group in acute pain, and in adults--in tonic pain. Thus, the data obtained in the rats with prenatal 5-HT deficiency and stress indicate involvement of 5-HT3 receptors in mediation of prolonged pain in the formalin test, and antinociceptive effect of ondansetron which is attenuated in animals with prenatal 5-HT deficiency and specifically depends on rat's age.

Role of the vagus nerves in neophobia and conditioned-reflex taste aversion.

Combination of ingestion of water with discomfort in rats with intact vagus nerves on selection between water and saccharine solution (an unknown taste) produced aversion not to water but to saccharine, with sharp increases in water consumption. In vagotomized rats, this combination led to a significant increase in saccharine consumption with no change in water intake. After extinction of neophobia to saccharine, combination of ingestion of water with rotation induced aversion to water in both groups (this being delayed in vagotomized rats). Vagus nerve signaling activity in selection conditions appears to determine the choice of behavior strategy.

[The role of the vagus nerves in the manifestations of neophobia and conditioned-reflex taste aversion]. / Rol' bluzhdaiushchikh nervov v proiavleniiakh neofobii i uslovnoreflektornoi vkusovoi aversii.

Vagotomized rats given a choice between water and an unfamiliar 0.2% saccharin solution ingest comparable amounts of both fluids over 2.5 weeks of testing. Saccharin intake in sham-operated rats grows steadily (attenuation of taste neophobia), with water intake being unchanged. After the pairing of water intake with rotation saccharin intake in vagotomized rats grows and in sham-operated animals decreases significantly, whereas water intake in the latter increases sharply. Thus, the rats with retained vagal innervation exhibit aversion to saccharin, substance with an unfamiliar taste, but not to water paired with a discomfort. After two-week elimination of neophobia to saccharin, the pairing of water intake with rotation brings into the acquisition of aversion to water in the first days of choice testing in sham-operated rats; similar aversion in vagotomized rats appears with retardation (on the 4th to 6th day).

[Sex dimorphism in the formation and extinction of aversion acquired to known and unknown tastes]. / Polovoi dimorfizm pri formirovanii i ugashenii aversii, vyrabatyvaemoi k znakomomu i neznakomomu vkusu.

One group of Wistar rats were taught to consume 0.2% solution of saccharin up to stable preference of the latter to water. The aversion was established by means of an angle acceleration rotation. This was preceded by feeding the saccharin solution unfamiliar to the second group of rats. The aversion formed more obviously in the second group animals. The data obtained is discussed from the standpoint of sexual characteristics of the taste preference, defence behaviour, ecological specifics of interaction of males and females with ambient milieu.

[Taste aversions in the ontogeny of the rat]. / Vkusovye aversii v ontogeneze krysy.

The characteristics of acquisition and extinction of conditioned taste aversion (CTA) were studied in rats of both sexes and various ages by pairing of saccharin solution consumption with discomfort (LiCl intoxication, rotation). Pairing of saccharin consumption with LiCl in adult rats led to acquisition of CTA, more profound in male rats than in female ones. In rats of both sexes 30 days old, a profound CTA, comparable in intensity with CTA of adult male rats was acquired. In 2 months after acquisition of CTA in adult rats its magnitude did not change, while in rats of the junior group which by that time had reached puberty, CTA was reduced in females and did not change in males. Pairing of saccharin intake and rotation led to acquisition of CTA only in rats 30 days old. The role of external factors in duration of retention of CTA acquired by pairing of saccharin solution consumption with LiCl injection was studied in male and female rats 1 and 3.5 months old. In all cases CTA was extinguished much sooner in home cages than in experimental chambers, and in the elder group sex dimorphism was found: in both situations CTA disappeared sooner in female rats. The obtained data allow to suggest modulating influences of hormonal background and of contextual stimuli on CTA acquisition and retention.