Effects of Injection of Gamma-Aminobutyric Acid Agonists into the Nucleus Accumbens on Naloxone-Induced Morphine Withdrawal

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 131-138 ◽  
Author(s):  
Betilay Topkara ◽  
Hasan R. Yananli ◽  
Eren Sakallı ◽  
Mahluga Jafarova Demirkapu
Keyword(s):  
Locomotor Activity ◽  
Nucleus Accumbens ◽  
Morphine Withdrawal ◽  
Aminobutyric Acid ◽  
Withdrawal Symptoms ◽  
Control Group ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Gaba Agonists ◽  
Sprague Dawley Rats

Aims: This study was to investigate the effects of local administration of gamma-aminobutyric acid (GABA) agonists into the nucleus accumbens (NAc) on naloxone-induced morphine withdrawal symptoms. Methods: Bilateral guide cannulas were stereotaxically implanted in the shell or core regions of the NAc of Sprague-Dawley rats. After a recovery period, 3 morphine pellets, each consisting of 75 mg morphine base, were placed subcutaneously on the first and third days of the study with the rats under mild ether anaesthesia. The GABA agonists, baclofen hydrochloride or muscimol hydrobromide, were injected into the NAc, and morphine withdrawal was induced by naloxone on the fifth day. Results: Administration of baclofen to the shell or core regions of the NAc of Sprague-Dawley rats led to statistically significant decreases in both behavioural and locomotor activity parameters during the morphine withdrawal period, compared to the control group. However, there were no statistically significant changes in locomotor activity or withdrawal behavioural parameters, with the exception of wet dog shakes, between control and muscimol-treated groups. Conclusion: These findings show that GABAergic conduction in the NAc is effective on the morphine withdrawal symptoms, and that both the shell and core regions of the NAc are associated with this effect.

Level of satiety: GABA and pentose shunt activities in three brain sites associated with feeding

1985 ◽  
Vol 248 (4) ◽  
pp. R453-R458 ◽  
Author(s):  
T. R. Kasser ◽  
R. B. Harris ◽  
R. J. Martin
Keyword(s):  
Area Postrema ◽  
Ventromedial Hypothalamus ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Energy Status ◽  
Sprague Dawley ◽  
Brain Areas ◽  
Gastric Intubation ◽  
Glucose Flux ◽  
Sprague Dawley Rats

The hypothesis addressed was that metabolic activity within specific brain areas may be altered to depict peripheral metabolic status. Sixty-three female Sprague-Dawley rats (225 g) received 150, 100, or 50% of normal intake by gastric intubation for 7 days. The incentive for spontaneous feeding would be inhibited in 150% fed rats (anoretic), stimulated in 50% fed rats (hungry), and maintained in 100% fed rats (control). Glucose flux through the gamma-aminobutyric acid shunt of the ventrolateral hypothalamus was 32% lower in hungry rats and 35% higher in anoretic rats relative to control values. Glucose flux through the pentose shunt of the ventromedial hypothalamus was 111% lower in hungry rats and 152% higher in anoretic rats relative to control values. Pentose shunt activity in the area postrema nucleus of the solitary tract (AP NTS) was 116% lower in hungry rats and 60% higher in anoretic rats relative to control values; however, hungry and anoretic rats had AP NTS pentose shunt activities that were not different from control values but were different from each other. The data demonstrate that within selective brain sites, specific pathways for glucose oxidation are affected by energy intake and may be used by the rat to assess and respond to changes in peripheral energy status.

scholarly journals Gamma Aminobutyric Acid-Enriched Fermented Oyster (Crassostrea gigas) Increases the Length of the Growth Plate on the Proximal Tibia Bone in Sprague-Dawley Rats

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4375
Author(s):  
Hyesook Lee ◽  
Hyun Hwangbo ◽  
Seon Yeong Ji ◽  
Min Yeong Kim ◽  
So Young Kim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Oral Administration ◽  
Growth Plate ◽  
Bone Health ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tibial Growth Plate ◽  
Igfbp 3

Bone growth during childhood and puberty determines an adult’s final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 μg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.

scholarly journals Functional observation after morphine withdrawal: effects of SJP-005

2021 ◽  
Author(s):  
Joris C. Verster ◽  
Andrew Scholey ◽  
Thomas A. Dahl ◽  
Jacqueline M. Iversen
Keyword(s):  
Early Phase ◽  
Late Phase ◽  
Morphine Withdrawal ◽  
Withdrawal Symptoms ◽  
Treatment Cessation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
New Treatment ◽  
Withdrawal Effects ◽  
Withdrawal Signs

Abstract Rationale and objective SJP-005 (ketotifen and ibuprofen) is being developed as a potential new treatment for opioid withdrawal. Three studies were conducted to evaluate the early phase (acute, day 1) and late phase (days 2–12) effects of SJP-005 on discontinuation-induced morphine withdrawal. Methods Sprague-Dawley rats received subcutaneous morphine twice daily for 18 days and ceased on day 19. Twice daily, oral dosages of placebo or SJP-005 (1 mg/kg ketotifen and 15 mg/kg ibuprofen) were administered starting 4 days before (study 1), 2 days before (study 2), or immediately after (study 3) morphine cessation. Functional observations were made up to 12 h after treatment cessation on day 19 (early phase), and immediately after treatment on days 20–30 (late phase). Treatment effects (mean overall score, and individual symptoms) were compared with placebo using ANOVA, and Tukey’s tests in case of multiple comparisons. Results Across the studies, the number of withdrawal signs on day 19 (early phase) and days 20–30 (late phase) was lower with SJP-005 compared with placebo. The effects of SJP-005 when treatment was initiated 2 days before morphine cessation by discontinuation were most pronounced and statistically significant in the late phase (F(1,18) = 14.10, p = 0.001). In particular, a significant reduction was observed in hypersensitivity to touch (F(1,18) = 13.65, p = 0.002). A 50% reduction in withdrawal symptoms was observed 9.0 days after placebo versus 4.5 days after SJP-005. After 9.0 days, all withdrawal symptoms were absent in the SJP-005 group, while symptoms in the placebo group were still evident on day 18. Conclusion Compared to placebo, SJP-005 significantly reduced the incidence and duration of discontinuation-induced morphine withdrawal symptoms when treatment was initiated 2 days before morphine cessation.

scholarly journals Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

2021 ◽  
Vol 18 (4) ◽  
pp. 1645
Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  
Keyword(s):  
Resistance Exercise ◽  
Endurance Exercise ◽  
Field Tests ◽  
Treadmill Running ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Sprague Dawley ◽  
Exercise Interventions ◽  
Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

Ranitidine as an alcohol dehydrogenase inhibitor in acute methanol toxicity in rats

2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek
Keyword(s):  
Alcohol Dehydrogenase ◽  
High Performance ◽  
Negative Control Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Sprague Dawley ◽  
Blood Samples ◽  
Methanol Poisoning ◽  
Sprague Dawley Rats

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.

scholarly journals CCK-8 and CCK-58 differ in their effects on nocturnal solid meal pattern in undisturbed rats

2012 ◽  
Vol 303 (8) ◽  
pp. R850-R860 ◽  
Author(s):  
Miriam Goebel-Stengel ◽  
Andreas Stengel ◽  
Lixin Wang ◽  
Gordon Ohning ◽  
Yvette Taché ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Molecular Forms ◽  
Reduce Food Intake ◽  
Dark Phase ◽  
Sprague Dawley ◽  
Solid Meal ◽  
Sprague Dawley Rats ◽  
And Behavior

Various molecular forms of CCK reduce food intake in rats. Although CCK-8 is the most studied form, we reported that CCK-58 is the only detectable endocrine peptide form in rats. We investigated the dark-phase rat chow intake pattern following injection of CCK-8 and CCK-58. Ad libitum-fed male Sprague-Dawley rats were intraperitoneally injected with CCK-8, CCK-58 (0.6, 1.8, and 5.2 nmol/kg), or vehicle. Food intake pattern was assessed during the dark phase using an automated weighing system that allowed continuous undisturbed monitoring of physiological eating behavior. Both CCK-8 and CCK-58 dose dependently reduced 1-h, dark-phase food intake, with an equimolar dose of 1.8 nmol being similarly effective (−49% and −44%). CCK-58 increased the latency to the first meal, whereas CCK-8 did not. The intermeal interval was reduced after CCK-8 (1.8 nmol/kg, −41%) but not after CCK-58. At this dose, CCK-8 increased the satiety ratio by 80% and CCK-58 by 160%, respectively, compared with vehicle. When behavior was assessed manually, CCK-8 reduced locomotor activity (−31%), whereas grooming behavior was increased (+59%). CCK-58 affected neither grooming nor locomotor activity. In conclusion, reduction of food intake by CCK-8 and CCK-58 is achieved by differential modulation of food intake microstructure and behavior. These data highlight the importance of studying the molecular forms of peptides that exist in vivo in tissue and circulation of the animal being studied.

Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

scholarly journals Synergistic suppression of pre-perfusion of donor livers with recipient serum and cobra venom factor treatment on hyperacute rejection following liver xenotransplantation

2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  
Keyword(s):  
Survival Time ◽  
Hyperacute Rejection ◽  
Cobra Venom ◽  
Control Group ◽  
Sprague Dawley ◽  
Donor Liver ◽  
Cobra Venom Factor ◽  
Sd Rats ◽  
Sprague Dawley Rats ◽  
And Control

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.

Systemic CI-966, a new γ-aminobutyric acid uptake blocker, enhances γ-aminobutyric acid action in CA1 pyramidal layer in situ

1990 ◽  
Vol 68 (9) ◽  
pp. 1194-1199 ◽  
Author(s):  
U. Ebert ◽  
K. Krnjević
Keyword(s):  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Acid Uptake ◽  
Sprague Dawley ◽  
Nipecotic Acid ◽  
Ca1 Region ◽  
Stratum Pyramidale ◽  
Sprague Dawley Rats ◽  
Pyramidal Layer ◽  
Urethane Anaesthesia

A new potent, blood–brain barrier permeable γ-aminobutyric acid (GABA) uptake blocker, 1-[2-[bis[4-(trifluoromethyl)-phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-966) was administered systemically by i.p. injection (5 mg/kg) in Sprague–Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there was a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region. Like the effect of nipecotic acid (applied locally by iontophoresis), the potentiation by CI-966 was clearest when GABA was applied in or near the stratum pyramidale where its action normally is weakest and shows the most pronounced fading. This change in GABA potency is most simply explained by a reduction in GABA uptake.Key words: GABA, muscimol, nipecotic acid, GABA-uptake blocker, epilepsy.

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