Brain contents of substance P, diazepam-binding inhibitor, and neuropeptide Y in high- and low-anxiety inbred rats during stress

The content of substance P in the hippocampus, hypothalamus, and midbrain of WAG/G rats surpassed these in Fischer-344 rats. After a 15-min stay in a shuttle box, the level of substance P in the hypothalamus and especially in the hippocampus decreased only in WAG/G rats. The content of diazepam-binding inhibitor in the hippocampus and midbrain of WAG/G rats was higher than in Ficher-344 rats. Stress increased the content of diazepam-binding inhibitor only in Fischer-344 rats. Midbrain content of neuropeptide Y in intact and stressed WAG/G rats was significantly lower than in Fischer-344 rats. There were no interstrain differences in the initial hypothalamic levels of neuropeptide Y between WAG/G and Fischer-344 rats. However, 15-min stress in the shuttle box increased hypothalamic content of neuropeptide Y only in Fischer-344 rats. Thus, high-anxiety rats are characterized by a low density of benzodiazepine receptors, decreased levels of substance P and diazepam-binding inhibitor, and high brain content of neuropeptide Y. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 254–257, September, 1999     

Role of inherent and individual acquired factors in the development of morphine sensitivity in WAG/G and Fischer-344 rats

Individual differences in sensitivity to morphine-induced suppression of vertical motor activity and analgesia in WAG/G and Fischer-344 rats are determined mainly by genetic factors, while sensitivity to morphine-induced suppression of total motor activity depends primarily on environmental factors. The severity of morphine dependence is determined predominantly by individually acquired factors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 535–538, May, 1998     

Effects of μ-, δ-, and κ-opioid agonists and enkephalinase inhibitor RB101 in two inbred rat strains

Analgesic and suppressive effects of selective μ- (DAGO), δ- (DME), and κ- (DAKLI) opioid agonists are compared with those of aminopeptidase N and neutral endopeptidase RB101 in rats of WAG/G and Fischer-344 rats. Fischer-344 rats were more susceptible to suppressive effects of DAGO and analgesic effect of DME. It is concluded that in these rats peculiarities of the μ- and δ-opioid systems determine susceptibility to locomotor depression and analgesia, respectively. There is no correlation between effects of DAGO and RB101 in these strains. This implies that depressive effect of RB101 is not mediated though μ-opioid systems. In contrast, the effects of DMA on pain sensitivity in WAG/G and F-344 rats are opposite to those of RB101. This suggests that specific features in the activity of cerebral δ-OS can determine the sensitivity of RB101-induced analgesia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 551–554, May, 1998     

Effect of Substance P on Intravenous Self-Administration of Morphine in Different Rat Strains

We studied the effects of substance P on intravenous self-administration of morphine in WAG/G and Fischer-344 rats. By the end of week 2 the daily amount of self-administered morphine in WAG/G rats was higher than in Fischer-344 rats. Treatment with substance P markedly suppressed self-injection of morphine, particularly in low doses. The most pronounced effects were observed in Fischer-344 rats. Substance P did not change food-procuring behavior of animals in the same experimental chambers. Since the content of substance P in the hippocampus, hypothalamus, and midbrain of Fischer-344 rats is much lower than in WAG/G rats, and morphine addiction in Fischer-344 rats is less pronounced than in WAG/G rats, the degree of opiate addiction is not determined by the content of substance P in rat brain. However, in our experiments treatment with substance P abolished morphine addiction, particularly in animals with low content of this compound in the brain.     

Participation of opioid and serotoninergic brain receptors in amphetamine-induced stereotypy and hyperthermy

The inbred rat strains WAG and Fischer-344 were found to differ in the duration of amphetamine-induced stereotypy and the degree of hyperthermy elicited by this drug, the stereotypy lasting longer in WAG rats and the hyperthermy being more pronounced in Fischer—344 rats. A comparison of interstrain differences in the amphetamine effects, in receptor binding, and in the pharmacological activity of receptor agonists suggests that the μ-opiate system of the brain may be involved in the manifestation of amphetamine-induced stereotypy, while its serotoninergic system may mediate the elevation of body temperature caused by this drug. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, 242–243, September, 1995 Presented by V. N. Yarygin, Member of the Russian Academy of Medical Sciences     

Variation in plasma morphine level and pain sensitivity in prenatally morphinized rats

It is established that mature random-bred and Wistar rats exhibit the same level of pain sensitivity in the tail-flick test, but the analgetic effect of morphine (5 mg/kg) is variously expressed: marked hypalgesia is observed in mongrel but not in Wistar rats. Prenatal morphinization enhances the analgetic effect of morphine in both mongrel and Wistar rats. There is a direct correlation between the plasma morphine content in prenatally morphinized rats and their sensitivity to the analgetic action of morphine. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 273–275, September, 1995 Presented by D. A. Kharkevich, Member of the Russian Academy of Medical Sciences     

Increased anxiety and reduced pain sensitivity in offspring of rats after prenatal morphinization

Administration of morphine to outbred female rats is shown to result in increased anxiety in the conflict test and reduced pain sensitivity in the tail flick test in 2.5-monthold offspring. In prenatally morphinized offspring the analgetic effect of morphine was enhanced, while the anxiolytic effect of buspirone was lower than in intact animals, which suggests rearrangements in the opioid and serotoninergic systems of the brain. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 154–156, August, 1994 Presented by M. D. Mashkovskii, Member of the Russian Academy of Medical Sciences     

Effects of acute and chronic caffeine intake on intravenous self-administration of morphine in two rat strains

Effects of acute and chronic caffeine intake on the level and pattern of morphine self-administration behavior in WAG/G and Fisher-344 rats were studied. Both acute and chronic caffeine intake decreased morphine self-administration only in WAG/G rats, which attested to increased sensitivity of these rats to reinforcing effects of morphine. Possible relationship between the observed changes and increased anxiety in rats receiving caffeine is discussed.     

Correlation of pain sensitivity and the humoral immune response in mice during thermal stimulation

A hypothesis about a correlation between threshold pain sensitivity and antibody production is proposed and experimentally validated. Immunodeficient mouse strains are characterized by a higher threshold sensitivity to pain than animals with a normal immune response. A highly reliable negative correlation between threshold sensitivity to pain assessed by the hot plate test and the number of antibody-producing cells in the spleen after immunization with sheep red cells is observed in 77% of (CBA×C57B1/6) F₁ mice examined. The negative correlation is observed both in spontaneous variations of threshold pain sensitivity and during an elevation of this threshold under the effect of preceding nociceptive stimulation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 4, pp. 405–408, April, 1995 Presented by R. V. Petrov, Member of the Russian Academy of Medical Sciences     

Chronobiological parameters of pain sensitivity of rats and mice

Circadian and 12-hour rhythms of pain sensitivity to stimuli of different origin were detected in male rats and mice by cosinor analysis in chronobiological experiments. The minimal pain sensitivity to thermal and electric stimulation was observed in rats during the first half of the light phase of 24 h, while in the case of mechanical stimulation it was observed during the dark phase. Biorhythms of sensitivity of mice and rats to thermal pain exposure were similar. Hence, the chronobiological organization of pain sensitivity depends mainly on the type of nociceptive stimulation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5, pp. 537–540, May, 1995     

Implication of the hippocampus in the development of a pain syndrome in rats following sciatic nerve damage

Local destruction or electrostimulation of the hippocampus did not affect pain sensitivity thresholds in rats with intact sciatic nerve. In rats with transected sciatic nerve, local hippocampal damage accelerated the development of a pain syndrome considerably, while hippocampal electrostimulation delayed it so that 80% of the test rats did not appear to have been experiencing pain throughout the 45-day observation period. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 120–122, August, 1994     

Lipid peroxidation and antioxidant enzymes in the brain of rats exposed to acute emotional stress: Effect of interleukin-1β

Acute emotional stress is shown to raise the level of malonic dialdehyde in the hypothalamus of August rats. After intraventricular administration of interleukin-1β, the malonic dialdehyde level and the activity of antioxidant enzymes tended to rise selectively in the hypothalamus (but not in the sensorimotor cortex) of August, Wistar, and WAG rats. In the presence of this interleukin, acute emotional stress did not cause increases in lipid peroxidation products in the hypothalamus of August rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 244–247, September, 1995     

Morphological manifestations of hereditary hypertrophic cardiomyopathy in W/SSM rats

A W/SSM strain of rats with hereditary hypertrophic cardiomyopathy has been created by inbreeding Wistar rats selected for an increased, sensitivity to the cataractogenic effect of high doses of galactose. It is shown that myocardial hypertrophy attended by a diffuse stroma collagenization, focal sclerotic changes, and signs of, chronic heart failure spontaneously develops in these animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 8, pp. 203–207, August, 1994     

The effect of etimyzol on the development of the deafferentation pain syndrome

Administration of etimyzol in a dose of 4 mg/kg to rats with deafferentation pain syndrome reduces the incidence of the syndrome and its severity. This effect is associated with activation of the hypothalamic-hypophyseal-adrenal system. Systematic administration of the preparation models repeated stress, thus developing adaptation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3 pp. 258–261, March, 1996 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Genetics of absence epilepsy in rats

All rats of the WAG inbred strain show electrophysiological and behavioral phenomena reminiscent of human absence epilepsy. To study the genetic architecture of this kind of epilepsy, WAG rats were cross bred with inbred ACI rats which show no signs of epilepsy. Number and duration of spike-wave discharges per hour were determined from 24-h recordings of cortical EEG in parental strains and reciprocal F₁ hybrids. All hybrids showed spike-wave discharges, indicating complete dominance for occurrence, but different genetic backgrounds were suggested for number and duration of the phenomena. These results imply that more than one gene is involved in absence epilepsy. Some genes determine the occurrence, while others may manipulate the actual number and duration of the epileptic phenomena.     

Spike Activity of Neurons in the Lateral Hypothalamus in Rats During Microiontophoretic Application of Melatonin and Noradrenaline

Microiontophoretic application of melatonin to the perineuronal space of nerve cells in the lateral hypothalamus of WAG and Fischer-344 rats led to decreases in the frequency and regularization of the spike activity of neurons, and also blocked activation of neurons and changing the patterns of adrenaline-induced spike activity. The effects of melatonin were more marked in WAG rats, which demonstrated the more active behavior in the open field test and were predicted to be more resistant to emotional stress, than in passive Fischer-344 rats, with predisposition to emotional stress. These results suggest that the mechanism of the stress-protective action of melatonin involves suppression of the spike activity of neurons in emotiogenic brain structures and changes in their sensitivity to noradrenaline.     

Assessment of immunotoxicity in female Fischer 344/N and Sprague Dawley rats and female B6C3F1 mice exposed to hexavalent chromium via the drinking water

Sodium dichromate dihydrate (SDD), an inorganic compound containing hexavalent chromium (Cr(VI)), is a common environmental contaminant of groundwater sources due to widespread industrial use. There are indications in the literature that Cr(VI) may induce immunotoxic effects following dermal exposure, including acting as both an irritant and a sensitizer; however, the potential immunomodulatory effects of Cr(VI) following oral exposure are relatively unknown. Following the detection of Cr(VI) in drinking water sources, the National Toxicology Program (NTP) conducted extensive evaluations of the toxicity and carcinogenicity of SDD following drinking water exposure, including studies to assess the potential for Cr(VI) to modulate immune function. For the immunotoxicity assessments, female Fischer 344/N (F344/N) and Sprague Dawley (SD) rats and female B₆C₃F₁ mice were exposed to SDD in drinking water for 28 consecutive days and evaluated for alterations in cellular and humoral immune function as well as innate immunity. Rats were exposed to concentrations of 0, 14.3, 57.3, 172, or 516?ppm SDD while mice were exposed to concentrations of 0, 15.6, 31.3, 62.5, 125, or 250?ppm SDD. Final mean body weight and body weight gain were decreased relative to controls in 250?ppm B₆C₃F₁ mice and 516?ppm SD rats. Water consumption was significantly decreased in F344/N and SD rats exposed to 172 and 516?ppm SDD; this was attributed to poor palatability of the SDD drinking water solutions. Several red blood cell-specific parameters were significantly (5–7%) decreased in 250?ppm mice; however, these parameters were unaffected in rats. Sporadic increases in the spleen IgM antibody response to sheep red blood cells (SRBC) were observed, however, these increases were not dose-dependent and were not reproducible. No significant effects were observed in the other immunological parameters evaluated. Overall, exposure to Cr(VI) in drinking water had limited effects on the immune system in both rats and mice.     

Immunological correlation between morphine tolerance and the effect of naloxone in rats of different age

In 3–6-week-old morphine-sensitive rats, in which morphine injection produced an analgetic effect, the serum titer of antimorphine antibodies 24 h postinjection is less than half that observed in morphine-resistant animals. Administration of naloxone to morphine-sensitive rats induces hyperalgesia and considerably raises the serum titer of antimorphine antibodies. Chronic injections of the same dose of morphine, which cause its analgetic effect to disappear, increase the titer of antibodies in morphine-sensitive rats 2-fold. In morphine-resistant rats naloxone produces an analgetic effect followed by its gradual decay and disappearance in the course of chronic administration. Subsequent administration of morphine induces analgesia, raises the titer of antimorphine antibodies, and lowers the titer of antiidiotypic antibodies. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 67–70, January, 1996 Presented by K. V. Sudakov, Member of the Russian Academy of Medical Sciences