Effect of Oxytocin on the Emotional State and Behavior of Rats under Stress Conditions

Oxytocin, a hormone exerting controlling effects on lactation, sexual and maternal behavior, and cyclic organization of sleep and wakefulness, is capable of significantly modulating reactions of the organism to the action of stressogenic stimuli. We studied the effects of injections of synthetic oxytocin on the behavioral phenomena and emotional state of rats during realization of a proconflict test induced by “punishments” (nociceptive electrical stimuli) in the process of drinking after water deprivation. Intraperitoneal injections of oxytocin in a 4.0 μg dose resulted in shortening of the delays of coming of rats to a water dish and also in an increase in the number of drinks of water punished by electrical stimulation, as compared with the corresponding indices in control animals. After oxytocin injections, the intensity of research activity of rats in the open field, in general, increased. After realization of the proconflict test, locomotor and orientational/research activities in animals preliminarily injected with oxytocin were much more intense than those in control rats (in the latter ones, these activities were sharply suppressed). Injections of oxytocin also led to certain normalization of the emotional state; after the proconflict test, negative shifts in this state in control rats were obvious. Therefore, oxytocin appreciably increases the resistivity of the organism against stress.     

Behavioral Activity and Anxiety of Rats under Open Field Conditions in the Norm and after Parenteral Introductions of Xenogenic Cerebrospinal Fluid

We studied the effects of injections of xenogenic cerebrospinal fluid (CSF) on behavioral phenomena in rats under open field conditions. Parenteral introduction of xenogenic liquor in adult male and female rats resulted in appreciable changes in the indices of spontaneous motor activity in the open field. Single and double CSF injections promoted intensification of motor and orientational/research activity followed by inhibition of the respective behavioral manifestations. Repeated CSF injections were accompanied by a gradual decrease in the behavioral activity of rats. In males and females, these changes were nearly synchronous. Injections of CSF also influenced the seasonal dynamics of behavioral phenomena in rats and cyclic changes in the activity of females during the estrous cycle. In the whole, CSF injections exerted more powerful effects than the action of main natural biological regulators (photoperiod and sex cycle). The presence of significant amounts of biologically active substances in the liquor, which are responsible for complex effects on links of the neuroendocrine regulatory system of recipients, is the probable basis of the revealed effects.     

Behavior of rats kept under conditions of a shifted light/dark regimen and receiving melatonin

We studied the effect of shift in the natural light/dark regimen (desynchronosis) and treatment with melatonin on behavioral characteristics of rats with different activity in the open-field test. Experiments were performed on 172 Wistar rats kept under conditions of the natural or shifted light/dark regimen. Some animals were intraperitoneally treated with 1 ml physiological saline or melatonin in doses of 1 and 2 mg/kg, while others did not receive the injections. Desynchronosis altered the normal rhythm of locomotor activity and abolished the differences between daytime and nighttime activity rats not receiving the injections. The influence of melatonin on locomotor activity of rats maintained under normal or shifted light/dark conditions depended on its dose, time of treatment, and initial behavioral characteristics of animals. Our results indicate that the use of melatonin for treatment of disturbances produced by a shift in the light/dark conditions should be performed taking into account individual behavioral characteristics of the organism.     

Features of the behavior of the rat with hereditarily determined arterial hypertension

The behaviour of spontaneously hypertensive rats (SHR strain), rats with inherited stress induced arterial hypertension (ISIAH, a new developed strain), and of their normotensive Wistar progenitors was studied. The open-field arena and a device for measuring the total activity in the home cage were used in the behavioural studies. The SHR were much more active in the open--field and home cage tests than the Wistar and ISIAH rats. The basal locomotor activity of the ISIAH strain was lower than that of the Wistar rats, but the ISIAH strain had an index of behavioural reactivity 2.7 fold higher than the Wistar or SHR strains. These behavioural characteristics corresponded to the hypertension patterns of the strains compared. Enhanced spontaneous locomotion of the SHR rats was associated with spontaneous increase in arterial blood pressure. The ISIAH rats showed low spontaneous locomotor activity, but high behavioural and blood pressure reactivity under conditions of mild emotional stress.     

Neuropharmacological analysis of interaction between galanin and glutamate receptors in the rat striatum

Bilateral injections of kainic acid (KA) in doses of 100 ng (but not of 20 ng) into the rat striatum caused behavioral disturbances, which were manifested as an increase in the latency of the movement initiation, a decrease in the indices of the locomotor activity in an “open field” test, an increase in muscle tone, and ptosis appearance. Intrastriatal bilateral administration of galanin (10 or 50 ng) decreased the number of crossing movements and rearings in the open field, without affecting the latency of the first crossing movement and the level of muscle tone, and with no ptosis. Combined administration of galanin (10, 20 or 50 ng) and KA (20 ng) into the striatum led to the dose-dependent emergence of behavioral disturbances, which resembled those caused by injections of 100 ng of KA into the caudate nuclei. Behavioral disturbances associated with intrastriatal injection of KA, galanin, and their combination were partially antagonized by naloxon, ketamine, and atropine. It is concluded that galanin potentiates specific behavioral effects of injected KA by modulation of receptors for endogenous opioids, excitatory amino acids, and acetylcholine.     

Effects of ethanol on locomotor and anxiety-like behaviors and the acquisition of ethanol intake in Lewis and spontaneously hypertensive rats

The purpose of the present study was to investigate whether Lewis (LEW) and spontaneously hypertensive rats (SHR), characterized in numerous behavioral tests as strains with high-anxiety and low-anxiety, respectively, could differ in their sensitivity to the effects of ethanol in the elevated plus maze (EPM) and the open field (OF), two classical models of anxiety/emotionality, as well as in the acquisition of ethanol drinking behavior. It was also of interest to examine the relationship between sweet and bitter fluids preference and ethanol intake. SHR and LEW rats were given saline or ethanol injections (0.6 or 1.2 g/kg, ip.) and tested in the EPM and OF. Subsequently the same animals were given continuous free choice between water and ethanol solution (2-8%). Additional groups of animals were exposed to a free-choice regimen between saccharin (0.002-0.09%) or quinine (0.0001-0.0015%) and water. The low dose of ethanol (0.6 g/kg) induced anxiolytic-like effects and intensive locomotor activation mainly in SHR rats tested in the OF arena. Overall, LEW counterparts were unaffected in OF test. In oral self-administration paradigm, SHR rats consumed significantly more ethanol than LEW rats. Concerning other solutions, SHR rats consumed large amounts of saccharin compared with LEW rats. These data indicate that the SHR preference for ethanol intake may be positively related to their differential sensitivity to the anxiolytic/stimulant effects of ethanol and to the sensitivity of this strain for saccharin reinforcement. In addition, these findings provide evidence that the SHR strain may represent a useful genetic and pharmacological tool to investigate ethanol drinking traits.     

Marker-assisted dissection of genetic influences on motor and neuroendocrine sensitization to cocaine in rats

This study investigated genetic influences on behavioral and neuroendocrine responses to cocaine sensitization. We used male and female rats of the inbred strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which display genetic differences in stress-related responses. The influence of two quantitative trait loci (QTL; Ofil1 and Ofil2 on chromosomes 4 and 7), which modulate stress reactivity in rats, on the effects of cocaine was also investigated through the use of recombinant lines (derived from a LEW   ×   SHR intercross) selected by their genotype at Ofil1 and Ofil2 . Animals were given repeated cocaine or saline injections and tested for locomotion (induction of sensitization). Two weeks later, all animals were challenged with cocaine, and locomotion and corticosterone levels were measured (expression of sensitization). Results indicated that male SHR rats showed more behavioral sensitization than LEW rats, whereas no strain differences in sensitization were seen among females. When challenged with cocaine, LEW and SHR rats of both sexes pretreated with cocaine showed behavioral sensitization compared with saline pretreated animals; however, only LEW rats displayed an increase in the corticosterone levels. Ofil1 was found to influence the induction of sensitization in males and Ofil2 modulated the locomotor effect of cocaine in females. This study provides evidence of a genotype-dependent relationship between the induction and expression of cocaine sensitization, and between the behavioral and neuroendocrine responses induced by cocaine. Moreover, the Ofil1 and Ofil2 loci may contain one or more genes that control the behavioral effects of cocaine in rats.     

Effects of intra-amygdaloid TRH injections on motor activity and dominant-submissive behavior in rats competing for water.

The effect of thyrotropin releasing hormone (TRH) microinjections into the central amygdala (10 g in 0.5 1 into each side) on locomotor activity water intake and dominance behavior in a water competition test was investigated in male Wistar rats. TRH increased the general motility without altering the number of rearings. Intra-amygdaloid TRH injection to submissive rats resulted in a loss of subordinate position in these animals in the water competition test. A tendency to decrease dominance followed the injection of the peptide to the dominant animals. The effect of TRH in the dominance test does not appear to involve influence on the thirst drive as microinjection of the peptide did not change significantly the water consumption in thirsty rats.     

Low dose of disulfiram and l-dopa evoked synergistic modification in behavior of Wistar and WAG/Rij rats

Comparative analysis of behaviors of two rat strains, Wistar and WAG/Rij, was performed. No behavioral differences between Wistar and WAG/Rij were found in the emotional resonance test. Disulfiram injection produced similar effects in both rat strains. Animals of the first group (with slow acquisition of emotional resonance reaction) transformed into the animals of the second group (with fast acquisition). Passive avoidance conditioning was successfully reproduced in Wistar and was significantly impaired in WAG/Rij. A low dose of disulfiram injected before or immediately after conditioning substantially improved the reproduction to a greater extent in WAG/Rij than Wistar strains thus eliminating in interstrain differences. Active avoidance conditioning was more successful in WAG/Rij than in Wistar rats However, on the next day conditioning in WAG/Rij was substantially impaired. Administration of the low dose of disulfiram or L-DOPA prior to conditioning impaired the acquisition but improved the reproduction on the following day in both strains, but disulfiram injection after conditioning improved conditioning in WAG/Rij to a greater extent than in Wistar. Thus, the pharmacologic enhancement of the reward system substantially changed animal behavior and improved memory consolidation.     

Impairment of the organization of locomotor and exploratory behaviors in bile duct-ligated rats

Hepatic encephalopathy (HE) arises from acute or chronic liver diseases and leads to several problems, including motor impairment. Animal models of chronic liver disease have extensively investigated the mechanisms of this disease. Impairment of locomotor activity has been described in different rat models. However, these studies are controversial and the majority has primarily analyzed activity parameters. Therefore, the aim of the present study was to evaluate locomotor and exploratory behavior in bile duct-ligated (BDL) rats to explore the spatial and temporal structure of behavior. Adult female Wistar rats underwent common bile duct ligation (BDL rats) or the manipulation of common bile duct without ligation (control rats). Six weeks after surgery, control and BDL rats underwent open-field, plus-maze and foot-fault behavioral tasks. The BDL rats developed chronic liver failure and exhibited a decrease in total distance traveled, increased total immobility time, smaller number of rearings, longer periods in the home base area and decreased percentage of time in the center zone of the arena, when compared to the control rats. Moreover, the performance of the BDL rats was not different from the control rats for the elevated plus-maze and foot-fault tasks. Therefore, the BDL rats demonstrated disturbed spontaneous locomotor and exploratory activities as a consequence of altered spatio-temporal organization of behavior.     

奖励性操作式条件反射任务在大鼠学习记忆研究中的应用

目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多（vs.Wistar＆Donepezil,P〈0.05）;单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多（vs.Wistar,P〈0.05）,奖赏获得次数减少（vs.Donepezil,P〈0.001）,反应准确率显著降低（vs.Wistar＆Donepezil,P〈0.05）;信号辨识任务中SHR组错误反应次数显著增多（vs.Wistar＆Donepezil,P〈0.05）,而反应准确率降低,组间差异有显著性（vs.Wistar＆Donepezil,P〈0.05）;消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[（1.0639±0.07086）mg/g]、乙酰胆碱[（2.7760±0.2609）μg/g]与五羟色胺[（1.2200±0.1137）μg/g]含量均显著低于Wistar组大鼠（P〈0.05）,多奈哌齐组大鼠乙酰胆碱含量显著增加[（3.9344±0.2747）μg/g]（vs.Wistar,P〈0.05;vs.SHR,P〈0.001）。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。     

Correction of arterial pressure in rats with hereditary hypertension by altering catecholamine metabolism in early ontogeny

In a newly developed rat strain with inherited stress-sensitive arterial hypertension (ISSAH) an attempt was made to reduce arterial blood pressure by L-DOPA injections during a short time period of the early ontogenesis. It was shown that L-DOPA injections to rats on days 7-9 or 14-16 of life had no effect. The same procedure performed on 21-23 or 21-25-day-old rats was followed by a decrease in the basal and stress-induced arterial blood pressure levels, measured in adulthood. Injections of dopamine-beta-hydroxylase inhibitor (FLA-59) with parallel L-DOPA administration completely blocked the blood pressure decreasing effect. It can be suggested that injections of L-DOPA in the 4th week of post-natal life reduce the blood pressure level in ISSAH rats by enhancing the rate of brain noradrenaline biosynthesis.     

Rat behavior in a light/dark chamber: place preference task

After a 6-week social isolation (from 22nd to 70th day from birth) male Wistar rats (a sibship, 10 animals), were tested for 20 min in a light/dark box in order to reveal behavioral features of choice of their spatial localization in unknown conditions. Socially deprived rats significantly differed from control animals in longer time of the room choice, higher number of entries of the light section, and higher number of rearings, which was probably explained by their higher anxiety and lack of experience to estimate unexpected stimuli and select a response. The mean level of behavioral activity during exploration of the box defined by the number of elementary operations per minute remained constant and was significantly higher in the socially deprived rats than in the control animals.     

Dopamine-dependent character of depressive-like behavior in WAG/Rij rats with genetic absence epilepsy

Placebo-treated WAG/Rij rats (as compared to normal Wistar rats without seizure pathology) exhibited depressive-like behavior similar to that of intact rats of the same strain: decreased exploratory activity in the open field test, increased immobility in the forced swimming test, decreased sucrose consumption and preference (anhedonia). Chronic injection of tricyclic antidepressant imipramine (15 mg/kg. i.p., for 15 days) exerted a therapeutic (antidepressant) effect on depressive-like behavior in WAG/Rij rats. After cessation of antidepressant therapy, the behavior of WAG/Rij rats didn't significantly differ from that of Wistar rats. Acute (single) injection of selective D2/D3 dopamine receptor antagonist raclopride (100 microg/kg, i.p., 15 min prior to behavioral testing) aggravated the symptoms of depressive-like behavior and suppressed antidepressant effect of chronic injection of imipramine in WAG/Rij rats, whereas it didn't exert a substantial effect on behavior of Wistar rats. Injection of D2/D3 dopamine receptor agonist Parlodel (bromocriptine) counteracted the depressive-like behavior in WAG/Rij rats and didn't exert substantial influence on behavior of Wistar rats with the exception of a decrease in immobility time in the forced swimming test. Injections of imipramine and raclopride didn't exert significant influences on the level of general locomotor activity and anxiety both in WAG/Rij and Wistar rats. The results demonstrate the dopamine-dependent character of depressive-like behavior in WAG/Rij rats, and indicate possible involvement of dopamine D2-like receptors in mediation of the antidepressant effect of imipramine on genetically determined depressive-like behavior in WAG/Rij rats.     

Prenatal and early postnatal dietary sodium restriction sensitizes the adult rat to amphetamines

Acute sodium deficiency sensitizes adult rats to psychomotor effects of amphetamine. This study determined whether prenatal and early life manipulation of dietary sodium sensitized adult offspring to psychomotor effects of amphetamine (1 or 3 mg/kg ip) in two strains of rats. Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) dams were fed chow containing low NaCl (0.12%; LN), normal NaCl (1%; NN), or high NaCl (4%; HN) throughout breeding, gestation, and lactation. Male offspring were maintained on the test diet for an additional 3 wk postweaning and then fed standard chow thereafter until testing began. Overall, blood pressure (BP), total fluid intake, salt preference, and adrenal gland weight were greater in SHR than in WKY. WKY LN offspring had greater water intake and adrenal gland weight than did WKY NN and HN offspring, whereas WKY HN offspring had increased BP, salt intake, and salt preference compared with other WKY offspring. SHR HN offspring also had increased BP compared with other SHR offspring; all other measures were similar for SHR offspring. The low-dose amphetamine increased locomotor and stereotypical behavior compared with baseline and saline injection in both WKY and SHR offspring. Dietary sodium history affected the rats' psychomotor response to the higher dose of amphetamine. Injections of 3 mg/kg amphetamine in both strains produced significantly more behavioral activity in the LN offspring than in NN and HN offspring. These results show that early life experience with low-sodium diets produce long-term changes in adult rats' behavioral responses to amphetamine.     

Folic Acid Prevents Behavioral Impairment and Na+,K+-ATPase Inhibition Caused by Neonatal Hypoxia–Ischemia

Folic acid plays an important role in neuroplasticity and acts as a neuroprotective agent, as observed in experimental brain ischemia studies. The aim of this study was to investigate the effects of folic acid on locomotor activity, aversive memory and Na(+),K(+)-ATPase activity in the frontal cortex and striatum in animals subjected to neonatal hypoxia-ischemia (HI). Wistar rats of both sexes at postnatal day 7 underwent HI procedure and were treated with intraperitoneal injections of folic acid (0.011 μmol/g body weight) once a day, until the 30th postnatal day. Starting on the day after, behavioral assessment was run in the open field and in the inhibitory avoidance task. Animals were sacrificed by decapitation 24 h after testing and striatum and frontal cortex were dissected out for Na(+),K(+)-ATPase activity analysis. Results show anxiogenic effect in the open field and an impairment of aversive memory in the inhibitory avoidance test in HI rats; folic acid treatment prevented both behavioral effects. A decreased Na(+),K(+)-ATPase activity in striatum, both ipsilateral and contralateral to ischemia, was identified after HI; a total recovery was observed in animals treated with folic acid. A partial recovery of Na(+),K(+)-ATPase activity was yet seen in frontal cortex of HI animals receiving folic acid supplementation. Presented results support that folic acid treatment prevents memory deficit and anxiety-like behavior, as well as prevents Na(+),K(+)-ATPase inhibition in the striatum and frontal cortex caused by neonatal hypoxia-ischemia.     

Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in rats

Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits.     

The influence of ZnCl2 injected into the neostriatum on locomotor behavior of rats

The influence of two-week daily microinjections of ZnCl2 into the rostral region of neostriatum on the locomotor behavior of Wistar rats in chronic experiments was studied. The 1-mcg dose of ZnCl2 decreased spontaneous locomotor activity in the "open field" and, beginning with the 5th day of microinjections, inhibited a shuttle-box conditioned avoidance reflex. The reflex recovered only in the first week after the injection withdrawal. The 0.1-mcg dose of ZnCl2 to a lesser extent affected the parameters of conditioned avoidance, whereas the level of spontaneous locomotor activity in this group of animals increased. The observed changes in rat behavior may be associated with the concentration-dependent influence of zinc ions on the ion channels in the membranes of neostriatum neurons, including glutamate activated. The possibility to control the activity of ion channels in a chronic behavioral experiment by zinc ion concentration is discussed.     

Anxiety and behavior in WAG/Rij strain rats with genetically induced absence attacks

Behavior of nonlinear rats and animals from Wistar and WAG/Rij (with inborn generalized absence epilepsy) strains was examined in the elevated plus-maze and the hole board. WAG/Rij rats demonstrated low exploratory behavior in both tests. In the elevated plus-maze, WAG/Rij rats were more balanced and more anxious than Wistar and nonlinear rats. Administration of ethosuximide completely eliminated spike-wave discharges but did not change behavioral interstrain differences. Since the spike-wave patterns develop in WAG/Rij at the age of 3 months, the behavior of young (2-moth-old) pups from different strains was compared and significant differences were revealed. Correlation between the genetically defined features (spike-wave discharges) and behavioral peculiarities in WAG/Rij rats is supposed.     

Early postnatal changes in sarcoplasmic reticulum calcium transport function in spontaneously hypertensive rats

This comparative study investigates the relationship between sarcoplasmic reticulum (SR) calcium(Ca²⁺)-ATPase transport activity and phospholamban (PLB) phosphorylation in whole cardiac homogenates of spo`ntaneously hypertensive rats (SHR) and their parent, normotensive Wistar Kyoto (WKY) strain during early postnatal development at days 1, 3, 6, 12 and at day 40 to ascertain any difference in SR Ca²⁺ handling before the onset of hypertension. At day 1, the rate of homogenate oxalate-supported Ca²⁺ uptake was significantly higher in SHR than in WKY (0.25 ± 0.02 vs 0.12 ± 0.01 nmoles Ca²⁺/mg wet ventricular weight/min, respectively; p < 0.001). This interstrain difference disappeared with further developmental increase in SR Ca²⁺ transport. Western Blot analysis and a semiquantitative ELISA did not reveal any difference in the amount of immunoreactive PLB (per mg of total tissue protein) between strains at any of the ages studied. In addition, levels of phosphorylated PLB formed in vitro in the presence of radiolabelled ATP and catalytic (C) subunit of protein kinase A did not differ between SHR and WKY at days 1, 3, 6 and 12. At day 40, C subunit-catalyzed formation of ³²P-PLB was reduced by 66% (p < 0.001) in SHR when compared to age-matched WKY In the early postnatal period between day 1 and 12 SR Ca²⁺-transport values were linearly related to the respective ³²P-PLB levels of both SHR and WKY rats. The results indicate that cardiac SR of SHR can sequester Ca²⁺ at a much higher rate immediately after birth compared to WKY rats. The disappearance of this interstrain difference with further development suggests that some endogenous neuroendocrine or nutritional factor(s) from the hypertensive mother may exert an influence upon the developing heart in utero resulting in a transiently advanced maturation of the SR Ca²⁺ transport function in SHR pups at the time of birth.