Administration Of Physiological Saline Research Articles

Hemorrhagic Activity of Cationic Starch Conjugates with Sterically Hindered Phenol after Intravenous Administration to Guinea Pigs.

Intravenous injection of cationic starch conjugated with sterically hindered phenol (terpenophenol) to guinea pigs did not increase hemorrhagic activity (in doses of 2 and 4 mg/kg) and plasma clotting time in activated partial thromboplastin time and prothrombin time tests (in a dose of 4 mg/kg) in comparison with administration of physiological saline. Intravenous injection of the cationic starch conjugate with the highest content of terpenophenol fragments (4.1%wt) in a dose of 2 mg/kg to guinea pigs leads to a decrease in hemorrhagic activity by 4 times in comparison with the control.

Intrathecal morphine exacerbates paresis with increasing muscle tone of hindlimbs in rats with mild thoracic spinal cord injury but without damage of lumbar α-motoneurons.

Adverse effects of morphine on locomotor function after moderate to severe spinal cord injury (SCI) have been reported; however, the effects after mild SCI without damage of lumbar α-motoneurons have not been investigated. We investigated the effects of lumbar intrathecal morphine on locomotor function after mild thoracic SCI and the involvement of classic opioid receptor activation. A mild thoracic contusive SCI was induced in adult rats at the T9-T10 spine level under sevoflurane anesthesia. We evaluated the effects of single doses of intrathecal morphine and selective μ-, δ-, and κ-opioid receptor agonists, continuous infusion of intrathecal morphine for 72 hours, and administration of physiological saline on locomotor function and muscle tone in the hindlimbs. The numbers of damaged and total α-motoneurons in the lumbar spinal cord were also investigated. Single doses of morphine aggravated residual locomotor function after SCI but did not affect functional recovery. Single doses of morphine and μ- and δ-opioid receptor agonists significantly aggravated residual locomotor function with increases in muscle tone after SCI, and the effects of the drugs were reversed by naloxone. In contrast, continuous infusion of morphine led to persistent decline in locomotor function with increased muscle tone, which was not reversed by naloxone, but did not increase the number of damaged lumbar α-motoneurons. These results indicate that a single dose of morphine at an analgesic dose transiently increases muscle tone of the hindlimbs via activation of spinal μ- and δ- opioid receptors, resulting in further deterioration of locomotor function in the acute phase of mild SCI. Our results also suggest that an increased dose of morphine with prolonged administration leads to persistent decline in locomotor function with increased muscle tone via mechanisms other than direct activation of classical opioid receptors. Morphine should be used cautiously even after mild SCI.

Conditioned place preference of kisspeptin-10

INTRODUCTION: Kisspeptins (KISS), a group of brain neuropeptides are involved in sexual behavior. KISS activate the hypothalamic neurons that synthesize gonadotropin releasing hormone. KISS was also detected in the limbic system. Earlier, we showed the activation of sexual motivation after the administration of kisspeptin-10 without increasing the level of testosterone in male rats, which suggests the extrahypothalamic effect of KISS.
 The aim of this work was to study the possibility of aquisition of conditioned place preference of kisspeptin-10, as well as to study the emotional and investigational behavior in rats after intranasal peptide administration.
 METHODS: Conditioned place preference test (CPP), open field test (OP) and elevated plus maze (EPM) were used in male Wistar rats.
 RESULTS: When studying CPP, animals spent 78.6 6.3% of the time in the chamber associated with the administration of KISS compared to control animals with administration of physiological saline (51.2% of the experiment time; p 0.05). After kisspeptin-10 administration locomotor activity was 2-fold increased (p 0.05), and the number of sniffings was 2-fold increased too (p 0.05). The parameters did not significantly differ in animals treated with kisspeptin or saline in PCL.
 CONCLUSION: Thus repeated intranasal administration of kisspeptin-10 induces the aquisition of CPP in rats. This suggests that kisspeptin-10 can cause activity in the reward system or the activation of brain regions associated with this system, which ultimately leads to the formation of an emotionally positive state.

Effects of a Trace Amine-Associated Receptor TAAR5 Agonist as a Model of Schizophrenia Using Electrocorticography Data from Rats

Chronic experiments on rats were run to evaluate the effects of the substance α-NETA, a trace amine-associated receptor TAAR5 agonist, on the electrocorticogram (ECoG). Changes in the spectral power of the main ECoG rhythms were assessed, as was spatial synchronization in the γ range, because of the role of γ oscillations in the transmission of information between regions presumptively affected in schizophrenia. Adult male Wistar rats underwent implantation of six nichrome electrodes into the cerebral cortex of both hemispheres in two rows of three, with the aim of assessing the topography of the whole cortex. A total of 20 experiments were conducted: animals in 10 experiments received systemic doses of α-NETA, while in the other 10 animals received physiological saline. Injections of α-NETA increased power in the δ range (0–5 Hz) and there was a linked decrease in power in the range 5–10 Hz. The greatest differences were seen in the first 10 min. No changes occurred after administration of physiological saline. Increases in slow waves were accompanied by decreases in spatial synchronization of γ oscillations between all six recording points from the pre-injection baseline as compared with controls. All effects were more marked in the anterior zones of the cortex. The results suggest that α-NETA alters dopamine transmission via infl uences on TAAR5, which in turn disrupts glutamatergic transmission, leading to dysfunction in γ synchronization, as occurs in schizophrenia.

Studies of the Role of Brain Melanocortin Receptors in Suppressing Food Consumption in Ether Stress in Mice

The melanocortin (MC) system controls food consumption in the resting state. Stress suppresses food consumption. It is not clear whether the brain MC system is involved in the development of stress anorexia in mice. The aim of the present work was to study the influences of pharmacological blockade and activation of brain MC receptors on food consumption on the background of stress. Mice (male C57Bl/6J) were subjected to ether stress (ether anesthesia for 0.5 min) before administration of physiological saline or a synthetic nonselective antagonist (SHU9119) or agonist (melanotan II) of MC receptors into the lateral ventricle. Food consumption in all mice was stimulated by prior 17-h starvation. Ether stress decreased food consumption and increased the blood corticosterone level and the hypothalamic AgRP gene mRNA (a natural antagonist of MC receptors) level 1 h after application. Pharmacological blockade of central MC receptors on the background of stress weakened stress anorexia and decreased the hypothalamic AgRP mRNA level, while activation exacerbated stress anorexia and hypercorticism. Thus, these studies showed that the central MC system is involved in the development of stress anorexia in mice.

Influence of the course of treatment by injections of ozonized saline on rheological properties of erythrocytes in patients with complex pathology

With help of comprehensive methods of piezodynamic aggregometry in a microvolume and gradient ektacytometry the study was carried out to evaluate rheological properties of erythrocyte in patients with complex pathology before and after each injection of ozonated physiological solution. It was shown that after administration of physiological saline and after each session of ozone therapy occurs reduction of minimum aggregates strength and rate of spontaneous aggregation like and microviscosity and increase of deformability and water permeability of erythrocyte membranes. Dynamics of changes in the studied parameters of erythrocytes shows the improvement of the rheological properties of blood in patients not only immediately after the procedure, but and after update of blood in 2 weeks, 1 and 2 months after the course.

Pharmacological Evidence that Histamine H3 Receptors Mediate Histamine-Induced Inhibition of the Vagal Bradycardic Out-flow in Pithed Rats.

In vivo stimulation of cardiac vagal neurons induces bradycardia by acetylcholine (ACh) release. As vagal release of ACh may be modulated by autoreceptors (muscarinic M2 ) and heteroreceptors (including serotonin 5-HT1 ), this study has analysed the pharmacological profile of the receptors involved in histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats. For this purpose, 180 male Wistar rats were pithed, artificially ventilated and pre-treated (i.v.) with 1mg/kg atenolol, followed by i.v. administration of physiological saline (1ml/kg), histamine (10, 50, 100 and 200μg/kg) or the selective histamine H1 (2-pyridylethylamine), H2 (dimaprit), H3 (methimepip) and H4 (VUF 8430) receptor agonists (1, 10, 50 and 100μg/kg each). Under these conditions, electrical stimulation (3, 6 and 9Hz; 15±3V and 1ms) of the vagus nerve resulted in frequency-dependent bradycardic responses, which were (i) unchanged during the infusions of saline, 2-pyridylethylamine, dimaprit or VUF 8430; and (ii) dose-dependently inhibited by histamine or methimepip. Moreover, the inhibition of the bradycardia caused by 50μg/kg of either histamine or methimepip (which failed to inhibit the bradycardic responses to i.v. bolus injections of acetylcholine; 1-10μg/kg) was abolished by the H3 receptor antagonist JNJ10181457 (1mg/kg, i.v.). In conclusion, our results suggest that histamine-induced inhibition of the vagal bradycardic out-flow in pithed rats is mainly mediated by pre-junctional activation of histamine H3 receptors, as previously demonstrated for the vasopressor sympathetic out-flow and the vasodepressor sensory CGRPergic (calcitonin gene-related peptide) out-flow.

Gender-Dependent Actions of the Histone Deacetylase Blocker Sodium Valproate on Olfactory Learning in 129Sv Mice during the Early Postnatal Period

The processes of histone acetylation in the brain underlie both the mechanisms supporting the long-term stable effects of early experience, transmitted to offspring generations by epigenetic inheritance, and learning. However, the role of acetylation in learning has previously been studied only in adult animals: high levels of learning can be linked with high levels of histone H3 acetylation in the brain. The role of acetylation processes in the mechanisms of early learning has not been addressed. We report here our studies of the effects of blockade of histone deacetylation with sodium valproate, which increases the level of acetylation of histone H3, on the outcome of training to olfactory discrimination in 8-day-old mice of strain 129Sv, which have low levels of learning with simulation of maternal grooming. Four doses of sodium valproate, given from day 3 to day 6 of postnatal development, were found to have gender-dependent actions: there were selective improvements in learning in males but not females, though females showed this seen after repeated administration of physiological saline. The possible epigenetic mechanisms underlying these gender-related differences are discussed.

Influence of ISDN, l-NAME and selenium on microcirculation, leukocyte endothelium interaction and angiogenesis after frostbite

BackgroundThe body of knowledge regarding the different facets of frostbite injury continues to expand. However, beside the administration of physiological saline, local rewarming, local disinfection and symptomatic medications, today no causal therapy is known which would accelerate angiogenesis and wound healing.The aim of this study was to investigate the influences of dilative acting drugs on microcirculation, angiogenesis and leukocyte behavior. Materials and MethodsEars of male hairless mice (n=40) were inflicted with full thickness frostbites using a cold air jet. Then the affects of four intraperitoneal injections of isosorbitdinitrate (ISDN, n=10), l-nitroarginine-methyl-ester (l-NAME, n=10), selenium (n=10) or sodium chloride (n=10; each administered to one of four corresponding study groups), on microcirculation, leukocyte-endothelial interaction and angiogenesis were investigated over a 12-day period using intravital fluorescent microscopy. ResultsAngiogenesis was most improved by ISDN (36.8 vs. 54.5% non-perfused area on day 3, 3.9 vs. 17.0% on day 7 compared to selenium, p<0.006). Venular diameter was most significantly dilated in the ISDN-group, l-NAME showed significantly decreased diameter over the complete time of 12 days. ISDN had positive influences on edema formation, which was significantly reduced compared to control (27% lower values compared to control; p=0.007 on day 3). The l-NAME-group showed the significant highest leukocyte-adhesion compared to control on days 7 and 12 (53% resp. 58% higher, p<0.006). ConclusionOverall, out of all the drugs tested, ISDN improved angiogenesis, dilated venules and decreased edema formation and therefore seems to have the greatest positive impact on these crucial parameters after frostbite injury.

Glutamatergic neurotransmission in the inferior colliculus influences intrastriatal haloperidol-induced catalepsy

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. In addition, it has also been implicated in the processing of acoustic information of aversive nature, as well as in sensory-motor gating. There is evidence that glutamate-mediated mechanisms at the IC level influence haloperidol-induced catalepsy. The present study investigated the influence of glutamate-mediated mechanisms in the IC on catalepsy induced by intrastriatal microinjection of haloperidol (10 μg/0.5 μl). Male Wistar rats received bilateral intracollicular microinjections of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 μl), the NMDA receptor antagonists MK-801 (15 or 30 nmol/0.5 μl) or physiological saline (0.5 μl), followed by bilateral microinjections of haloperidol (10 μg/0.5 μl) or vehicle (0.5 μl) into the dorso-rostral or ventro-rostral striatum. The catalepsy test was performed positioning both forepaws of the rats on an elevated horizontal wooden bar and recording the time during which the animal remained in this position. The results showed that the administration of physiological saline in the IC followed by the microinjection of haloperidol in the dorso-rostral region of the striatum was not able to induce catalepsy. However, when the bilateral administration of NMDA into the IC was followed by microinjection of haloperidol into the dorso-rostral striatum, catalepsy was observed. The microinjection of haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by previous administration of MK-801 into the IC. These findings suggest that glutamate-mediated mechanisms in the IC can influence the intrastriatal haloperidol-induced catalepsy and that the IC plays an important role as a sensorimotor interface.

Anti-Fatigue Effects of Polysaccharides from &lt;i&gt;Gynostemma pentaphyllum&lt;/i&gt; Makino by Forced Swimming Test

The current study was designed to investigate the anti-fatigue effects of polysaccharide ofGynostemma pentaphyllumMakino (GMP). The mice were randomly divided into four groups: control group, low-dose GMP-treated group, middle-dose GMP-treated group and high-dose GMP-treated group. The animals of control group received an oral administration of physiological saline in a volume of 1.0 mL, and the animals of treated group received the same volume of GMP (50, 100 and 200 mg/kg bodyweight/day) for 28 days. After 28 days, anti-fatigue effects of GMP were assessed by forced swimming test and some biochemical parameters related to fatigue including blood lactic acid (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), glutathione peroxidase (GPH-Px), liver glycogen and muscle glycogen were measured using commercial kits. The results demonstrated that GMP prolonged the exhaustive swimming time, increased the liver glycogen and muscle glycogen contents, and decreased the BLA and BUN levels. It also improved the SOD and GPH-Px activities in blood of mice. These results indicated that FPR had anti-fatigue effects.

Salvianolic acid A promotes the acceleration of neovascularization in the ischemic rat myocardium and the functions of endothelial progenitor cells

Ethnopharmacological relevanceSalvia miltiorrhiza (SM, also known as DanShen) is one of the well-known widely used Chinese herbal medicines in clinical, containing phenolic compounds and potent antioxidant properties. Salvianolic acid A (SAA) is the most potent component of SM. A modern experimental strategy for treating myocardial ischemia is to induce neovascularization of the heart by the use of "angiogens", mediators that induce the formation of blood vessels, or angiogenesis. Studies demonstrated that coronary collateral vessels protect ischemic myocardium after coronary obstruction; therefore, we sought to examine whether SAA could stimulate myocardial angiogenesis. Materials and methodsMale Sprague–Dawley rats myocardial infarct (MI) induced by ligation of left anterior descending coronary artery (LAD) were randomly divided into five groups: sham-operated group; LAD occlusion + administration of physiological saline (vehicle treated group); LAD occlusion + administration of different concentrations of SAA (10, 5.0 and 2.5mg/kg/d). Infarct size and capillary density in the infarct region were measured with a previous experimental method. Immunohistological analysis was performed to measure vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR-2) expressions. The secretion of matrix metalloproteinase type X (MMP-9) was evaluated in serum of post-ischemic rats. We also performed the experiments of SAA on rat endothelial progenitor cells (EPCs) numbers and the capacity of migration and vasculargenesis. ResultsSAA potentiated the ischemia-induced neovascularization after 1week post-operation when compared to vehicle treated group. This effect could be attributed to an increased formation of VEGF, VEGFR-2, and MMP-9 as well as the promotion of numbers and functions of EPCs. ConclusionThese findings show that SAA has potent proangiogenic properties by promoting the expression of proangiogenic factors, and the functions of EPCs, indicating that SAA might contribute to the protective effect against coronary disease. Chemical compound studied in this paper is salvianolic acid A (PubChem CID: 5281793)

P.1.g.067 Tianeptine has neuroprotective effects in a differentiated SH-SY5Y human neuroblastoma cell line

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. In addition, it has also been implicated in the processing of acoustic information of aversive nature, as well as in sensory-motor gating. There is evidence that glutamate-mediated mechanisms at the IC level influence haloperidol-induced catalepsy. The present study investigated the influence of glutamate-mediated mechanisms in the IC on catalepsy induced by intrastriatal microinjection of haloperidol (10 μg/0.5 μl). Male Wistar rats received bilateral intracollicular microinjections of the glutamate receptor agonist NMDA (10 or 20 nmol/0.5 μl), the NMDA receptor antagonists MK-801 (15 or 30 nmol/0.5 μl) or physiological saline (0.5 μl), followed by bilateral microinjections of haloperidol (10 μg/0.5 μl) or vehicle (0.5 μl) into the dorso-rostral or ventro-rostral striatum. The catalepsy test was performed positioning both forepaws of the rats on an elevated horizontal wooden bar and recording the time during which the animal remained in this position. The results showed that the administration of physiological saline in the IC followed by the microinjection of haloperidol in the dorso-rostral region of the striatum was not able to induce catalepsy. However, when the bilateral administration of NMDA into the IC was followed by microinjection of haloperidol into the dorso-rostral striatum, catalepsy was observed. The microinjection of haloperidol into the ventro-rostral striatum induced catalepsy, counteracted by previous administration of MK-801 into the IC. These findings suggest that glutamate-mediated mechanisms in the IC can influence the intrastriatal haloperidol-induced catalepsy and that the IC plays an important role as a sensorimotor interface.

Ambroxol Alleviates Hepatic Ischemia Reperfusion Injury by Antioxidant and Antiapoptotic Pathways

BackgroundHepatic ischemia/reperfusion (HI/R) injury is a common pathologic process caused by many clinical settings, such as liver resection, liver transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts as a mucolytic agent, provides antioxidant and anti-inflammatory effects. MethodsA rat model of HI/R was induced by clamping the hepatic artery, the hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes followed by reperfusion for 6 hours under anesthesia. The sham group underwent laparotomy without hepatic ischemia. The ambroxol group was injected into the tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80 mg/kg, or 140 mg/kg. The control group underwent the same procedure as the ambroxol group but with administration of physiological saline. Liver injury was evaluated by biochemical and histopathological examinations. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3, Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK) we estimated activation. ResultsWistar rats that received 20, 80 mg or 140 mg of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol reduced the histologic injury and significantly decreased serum ALT and AST levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group, Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P < .05). ConclusionThese results indicated that ambroxol attenuated rat HI/R through upregulation of intracellular antioxidant and anti-apoptotic signaling pathways.

Influence of anti-inflammatory and vasoactive drugs on microcirculation and angiogenesis after burn in mice

Objective The treatment of burns remains a challenge. Besides the administration of physiological saline, local disinfection and symptomatic medications, no causal therapy is known to accelerate angiogenesis and wound healing. The aim of this study was to investigate the influences of dilatative and anti-inflammatory acting drugs on microcirculation, angiogenesis and leukocyte behavior, which had shown positive effects in former burn studies. Methods The ears of male hairless mice ( n = 47) were inflicted with full thickness burns using a hot air jet. Then the affects of five intraperitoneal injections of either acetylsalicylic acid (ASA), isosorbide dinitrate, prostaglandin E1 (PGE1) or sodium chloride (each administered to one of four corresponding study groups), on microcirculation, leukocyte-endothelial interaction and angiogenesis were investigated over a 12 day period using intravital fluorescent microscopy. Results Angiogenesis was slightly improved by PGE1 (0.3 vs. 1.3% non-perfused area in other groups on day 12, p = 0.029). Additionally, blood flow increased and rolling leukocytes decreased compared to other groups. The ASA-group showed best functional vessel density and lowest leukocyte-adhesion. The often described posttraumatic expansion of tissue damage could not be observed in either group. Conclusion Prostaglandin E1 improved angiogenesis, increased the blood flow and reduced the number of rolling leukocytes. ASA had positive influences on functional vessel density, edema formation and the number of sticking leukocytes. However, it reduced the blood flow. Overall, out of all the drugs tested, prostaglandin seems to have the greatest positive impact on microcirculation and angiogenesis in burns.

Spinal sumatriptan inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT 1B rather than 5-HT 1D receptors

Migraine is a neurovascular disorder associated with trigeminal activation, vasodilatation and trigeminal release of calcitonin gene-related peptide (CGRP). The antimigraine properties of triptans may be due to: i) vasoconstriction of the carotid arterial bed via 5-HT 1B receptors; and ii) inhibition of CGRP release from trigeminal nerves, via 5-HT 1B/1D receptors. This study investigated the effects of intrathecally administered sumatriptan (a 5-HT 1B/1D receptor agonist) and PNU-142633 (a 5-HT 1D receptor agonist) on the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine. For this purpose, 42 mongrel dogs were anaesthetised with sodium pentobarbitone and, subsequently, vagosympathectomized. The animals were prepared to measure arterial blood pressure, heart rate and external carotid blood flow; the thyroid artery was cannulated for infusion of agonists. 1-min intracarotid (i.c.) continuous infusions of capsaicin, α-CGRP and acetylcholine produced dose-dependent increases in external carotid blood flow without affecting arterial blood pressure or heart rate. These vasodilator responses remained unaffected after intrathecal (i.t.) administration of physiological saline (0.5 ml) or PNU-142633 (300–1000 μg); in contrast, i.t. sumatriptan (300–1000 μg) significantly inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. Furthermore, i.t. administration of SB224289 (a 5-HT 1B receptor antagonist), but not of BRL15572 (a 5-HT 1D receptor antagonist), abolished the above inhibition by sumatriptan. These results suggest that sumatriptan-induced inhibition of the external carotid vasodilatation to capsaicin involves a central mechanism mainly mediated by 5-HT 1B receptors.

Comparative analysis of the expression of c-Fos and interleukin-2 proteins in hypothalamus cells during various treatments

The aim of the present work was to perform a combined analysis of the degree of activation of the anterior hypothalamus of the rat and expression of the interleukin-2 gene during treatments of different types: mild stress ("handling") and adaption to it, as well as intranasal administration of physiological saline and the peptides Vilon (Lys-Glu) and Epitalon (Ala-Glu-Asp-Gly). Changes in the numbers of c-Fos-and IL-2-positive cells in structures of the lateral area (LHA) and anterior (AHN), supraoptic (SON), and paraventricular (PVN) nuclei of the hypothalamus in Wistar rats. Ratios of the quantities of c-Fos-and IL-2-positive cells were determined in intact animals and after activation of brain cells initiated by different treatments; the influences of adaptation to handling on the nature of changes in the expression of these proteins was also studied. Combined analysis of the intensity of expression of these two proteins - c-Fos, a marker of neuron activation and a trans-factor for the IL-2 cytokine gene and other inducible genes, and IL-2 - in intact animals and after various treatments showed that the process of cell activation in most of the hypothalamic structures studied correlated with decreases in the quantity of IL-2-positive cells in these structures; different patterns of changes in the numbers of c-Fos-and IL-2-positive cells were seen in response to different treatments in conditions of stress and adaptation to it.

PRECLINICAL STUDY: Chronic deep brain stimulation in the rat nucleus accumbens and its effect on morphine reinforcement

In order to explore a novel method for the treatment of drug abuse, we evaluated the effect of chronic deep brain stimulation (DBS) of the rat nucleus accumbens (NAc) on morphine reinforcement, using a DBS apparatus and an implant method we developed. Thirty-two adult rats weighing 240-260 g were divided into three groups, which included a DBS group (n = 10, administration of surgery, morphine and DBS), a sham DBS group (n = 12, administration of surgery and morphine) and a control group (n = 10, administration of physiological saline). The DBS electrode was stereotaxically implanted into the core of unilateral NAc and connected to an implantable pulse generator. Then, they were fixed to the rat skull. One week later, the rats in each group were intraperitoneally injected with morphine at an increasing dose (10-60 mg/kg) once daily. The rats in the DBS group were administered a 130-Hz high-frequency stimulation (HFS) once daily. A 900-second conditioned place preference (CPP) paradigm was used for determining the effect of electrical stimulation on morphine reinforcement in rats. The data showed that 7-10 days later, the preference score of the DBS group was significantly lower than that of the sham DBS group. The results suggest that chronic HFS of the rat NAc can block CPP induced by morphine and attenuate morphine reinforcement.

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.

Hematological Parameters in Wistar Rats in Conditions of Stress and Treatment with Heparin

The effects on hematological measures of emotional tension arising during the formation of food-procuring behavior in a multiple-choice maze and in conditions of pain (injection of 0.85% physiological saline i.m., 0.3 ml, daily for five days) were studied in Wistar rats. Physiological saline and training of intact animals led to increases in RBC volume and mean corpuscular hemoglobin content, accompanied by significant increases in plasma corticosterone levels. At the same time, neither heparin (standard unfractionated heparin, Serva, doses of 64 and 640 IU/kg, daily for five days) nor training of heparinized rats produced any changes in these measures. The high levels of organization of the acquired behavior and the working capacity seen in heparinized rats were evidence for improvements in both the associative properties of conditioned reflex activity and the mechanisms supporting stable reproduction of the acquired habit. After administration of heparin, rats lost all types of manifestation reflecting psychoemotional tension as generally seen in animals in the active (administration of physiological saline) and passive (intact rats) controls.