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.

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.

A new way to treat morphinism

1930 ◽  
Vol 26 (10) ◽  
pp. 1056-1056
Author(s):  
M. Sokel
Keyword(s):  
Morphine Withdrawal ◽  
Withdrawal Symptoms ◽  
New Treatment

Abstracts. Neuropathology and Psychiatry. Dr. M. Sokel describes (D. m. W. 1930, no. 42) a new treatment for morphinism. With the sudden withdrawal of morphine to avoid the phenomena of morphine withdrawal a. in the first 6-8 days he injected a large amount of insulin (up to 80 units of insulin "Leo" in 24 hours) without wine. Sahara. The amount of insulin depended on the severity of the withdrawal symptoms. A total of 15 patients were treated.

Effects of 4-h ischemia and 1-h reperfusion on rat muscle sarcoplasmic reticulum function

2001 ◽  
Vol 281 (4) ◽  
pp. E867-E877 ◽  
Author(s):  
R. Tupling ◽  
H. Green ◽  
G. Senisterra ◽  
J. Lepock ◽  
N. McKee
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Phase 1 ◽  
Late Phase ◽  
Maximal Activity ◽  
Hill Coefficient ◽  
Sprague Dawley ◽  
Rapid Phase ◽  
Sprague Dawley Rats ◽  
The Hill

To investigate the hypothesis that ischemia and reperfusion would impair sarcoplasmic reticulum (SR) Ca2+ regulation in skeletal muscle, Sprague-Dawley rats ( n = 20) weighing 290 ± 3.5 g were randomly assigned to either a control control (CC) group, in which only the effects of anesthetization were studied, or to a group in which the muscles in one hindlimb were made ischemic for 4 h and allowed to recover for 1 h (I). The nonischemic, contralateral muscles served as control (C). Measurements of Ca2+-ATPase properties in homogenates and SR vesicles, in mixed gastrocnemius and tibialis anterior muscles, indicated no differences between groups on maximal activity, the Hill coefficient, and Ca50, defined as the Ca2+concentration needed to elicit 50% of maximal activity. In homogenates, Ca2+ uptake was lower ( P < 0.05) by 20–25%, measured at 0.5 and 1.0 μM of free Ca2+ ([Ca2+]f) in C compared with CC. In SR vesicles, Ca2+ uptake was lower ( P < 0.05) by 30–38% in I compared with CC at [Ca2+]f between 0.5 and 1.5 μM. Silver nitrate induced Ca2+ release, assessed during both the initial, early rapid ( phase 1), and slower, prolonged late ( phase 2) phases, in homogenates and SR vesicles, indicated a higher ( P < 0.05) release only in phase 1in SR vesicles in I compared with CC. These results indicate that the alterations in SR Ca2+ regulation, previously observed after prolonged ischemia by our group, are reversed within 1 h of reperfusion. However, the lower Ca2+ uptake observed in long-term, nonischemic homogenates suggests that altered regulation may occur in the absence of ischemia.

Autogenous transplants of adrenal fragments in an animal model.

2018 ◽  
Vol 90 (4) ◽  
pp. 23-28 ◽  
Author(s):  
Agnieszka Dworzyńska ◽  
Katarzyna Paduszyńska ◽  
Lech Pomorski
Keyword(s):  
Adrenal Gland ◽  
Adrenal Insufficiency ◽  
Adrenal Glands ◽  
Bilateral Adrenalectomy ◽  
Adrenal Tumors ◽  
Human Beings ◽  
Sprague Dawley ◽  
The Third ◽  
Sprague Dawley Rats ◽  
New Treatment

Introduction Adrenal insufficiency is a typical complication after surgical treatment of adrenal tumors, especially after the removal of both adrenal glands. Human beings are not able to survive without adrenal glands and without proper hormonal substitution. Autotransplantation of a fragment of the adrenal gland may prevent this complication. This can be done by transplanting the entire adrenal glands or its fragment, such as the adrenal cortex cells. In the case of adrenal tumors, the entire adrenal gland can not be transplanted. However, it is possible to transplant cells from the tumor-free part. Succesful adrenal autografts may result in a new treatment of adrenal insufficiency. Materials and Methods: Autograft transplantation was performed on 3 groups of Sprague Dawley rats. In the first group, physiological corticosterone concentrations were determined. These animals were not operated. In the second group, both adrenal glands were removed. Corticosterone concentrations were determined after bilateral adrenalectomy. The third group was divided into two parts. In the first subgroup, bilateral adrenalectomy was performed simultaneosly with adrenal transplant into the omentum. In the second subgroup, right adrenalectomy was performed simultaneosly with and adrenal transplant into the omentum followed a month later by left adrenalectomy. During the experiment, corticosterone concentrations were measured at 4 time points. Results. The statistical difference between corticosterone concentrations in rats after two timed adrenalectomies and rats after bilateral adrenalectomy was statistically different, but these results were far from physiological concentrations.

Testosterone, dihydrotestosterone, androstenedione and dehydroepiandrosterone concentrations in placentae, ovaries and plasma of the rat in late pregnancy

1984 ◽  
Vol 105 (1) ◽  
pp. 119-125 ◽  
Author(s):  
C. Legrand ◽  
J. Marie ◽  
J. P. Maltier
Keyword(s):  
Similar Pattern ◽  
Sharp Increase ◽  
Late Phase ◽  
Late Pregnancy ◽  
Sprague Dawley ◽  
Ovulatory Cycle ◽  
Peripheral Plasma ◽  
Sprague Dawley Rats

Abstract. Testosterone (T), dihydrotestosterone (DHT), androstenedione (Δ4) and dehydroepiandrosterone (DHA) were measured by radioimmunoassay in peripheral plasma, uterine vein plasma, ovary and placentae within the last 3–4 days of pregnancy in Sprague-Dawley rats. In the uterine vein, T and Δ4 levels were significantly higher than those reported in the peripheral plasma at any particular day of late pregnancy. In peripheral plasma as in uterine vein plasma Δ4 and T gradually decreased from day 20 to term (−63% for Δ4 and approximately −45% for T) whereas DHT concentrations were unchanged. This decline is concomitant with a similar pattern of change in the placentae; indeed placental concentrations of Δ4 and T decreased significantly from day 19 to 22 (−63 and −79%, respectively) and were positively correlated with the levels of both androgens in uterine venous and peripheral plasma. Thus it was concluded that in the late phase of pregnancy in the rat circulating Δ4 and T originate from placentae. In contrast, ovarian androgen concentrations showed a sharp increase from day 21 to term: 58% for DHA, 49% for Δ4, 87% for T and 24% for DHT. It is suggested that these increasing concentrations of ovarian androgens could be related to the next ovulatory cycle.

scholarly journals PGE2suppresses mitogen-induced Ca2+mobilization in T cells

1999 ◽  
Vol 277 (6) ◽  
pp. R1741-R1748 ◽  
Author(s):  
Mashkoor A. Choudhry ◽  
Philip E. Hockberger ◽  
Mohammed M. Sayeed
Keyword(s):  
T Cells ◽  
Plasma Membrane ◽  
T Cell ◽  
Late Phase ◽  
T Cell Proliferation ◽  
Resting Cells ◽  
Sprague Dawley ◽  
Con A ◽  
Sprague Dawley Rats ◽  
Intracellular Ca

PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+signaling. The present study evaluated the effects of PGE2on Ca2+release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+imaging technique, and the release of Ca2+from intracellular stores and Ca2+influx were spectrofluorometrically quantified in T cell suspensions. Under unstimulated conditions, nearly 85% of T cells exhibited [Ca2+]i≤50 nM. After stimulation with concanavalin A (Con A), an increase in [Ca2+]iwas recorded in ∼60% of the cells. The pretreatment of T cells with PGE2had no apparent effect on [Ca2+]iin resting cells; it significantly suppressed the Con A-induced increase in [Ca2+]iin all of the Con A-responsive cells. Ca2+release from the intracellular stores contributed to the early spike in [Ca2+]i, and the late phase of elevation in [Ca2+]iwas dependent on Ca2+influx through the plasma membrane. Our data suggest that PGE2causes an overall suppression of the Con A-induced [Ca2+]ielevation in T cells via inhibiting both Ca2+influx and its release from the intracellular stores.

scholarly journals N-Oleoylglycine and N-Oleoylalanine Do Not Modify Tolerance to Nociception, Hyperthermia, and Suppression of Activity Produced by Morphine

2021 ◽  
Vol 13 ◽  
Author(s):  
Erin M. Rock ◽  
Cheryl L. Limebeer ◽  
Megan T. Sullivan ◽  
Marieka V. DeVuono ◽  
Aron H. Lichtman ◽  
...  
Keyword(s):  
Behavioral Responses ◽  
Morphine Tolerance ◽  
Opiate Dependence ◽  
Male Rats ◽  
Sprague Dawley ◽  
Endogenous Fatty Acid ◽  
Analgesic Effects ◽  
Fatty Acid Amides ◽  
Sprague Dawley Rats ◽  
Withdrawal Effects

The endogenous amide N-Oleoylglycine (OlGly) and its analog N-Oleoylalanine (OlAla), have been shown to interfere with the affective and somatic responses to acute naloxone-precipitated MWD in male rats. Here we evaluated the potential of a single dose (5 mg/kg, ip) which alleviates withdrawal of these endogenous fatty acid amides to modify tolerance to anti-nociception, hyperthermia, and suppression of locomotion produced by morphine in male Sprague-Dawley rats. Although rats did develop tolerance to the hypolocomotor and analgesic effects of morphine, they did not develop tolerance to the hyperthermic effects of this substance. Administration of neither OlGly nor OlAla interfered with the establishment of morphine tolerance, nor did they modify behavioral responses elicited by morphine on any trial. These results suggest that the effects of OlGly and OlAla on opiate dependence may be limited to naloxone-precipitated withdrawal effects.

Biodistribution of N-lsopropyl-p-lodoamphetamine in the Rat Brain

1987 ◽  
Vol 26 (03) ◽  
pp. 131-134 ◽  
Author(s):  
S. Jinnouchi ◽  
K. Watanabe ◽  
T. Ueda ◽  
K. Kinoshita ◽  
T. Yamaguchi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
White Matter ◽  
Rat Brain ◽  
Perfusion Imaging ◽  
Early Phase ◽  
Cerebral Perfusion ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
The Brain

The biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was studied in the rat brain.131 l-labelled IMP was injected intravenously in awake animals. Activities in the brain of Sprague-Dawley rats were 2.68–3.22 (% dose/g) in the cortex and 0.59–0.66 (% dose/g) in the white matter at 1 min p. i. Activities in the cortex were slightly increased at 60 min p. i., while activities in the white matter increased markedly at 60 min and 6 h p. i. Therefore, the cerebral cortex-to-white matter ratio decreased from 5 to 1 within 60 min after injection. Autoradiograms of the rat brain at 1–10 min p. i. showed high contrasts. Activities were high in the cortex and low in the white matter, but homogeneous at 60 min – 6 h. IMP seems to be a useful agent for cerebral perfusion imaging in the early phase after injection. Knowledge of biodistribution of this agent is considered to be indispensable for the interpretation of images.

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