Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat

2018 ◽  
Vol 52 (6) ◽  
pp. 588-598 ◽  
Author(s):  
Mario Arenillas ◽  
Ignacio A Gomez de Segura
Keyword(s):  
Aqueous Solubility ◽  
General Anaesthetic ◽  
Sprague Dawley ◽  
Similar Time ◽  
Wide Margin ◽  
Analgesic Effects ◽  
Sprague Dawley Rats ◽  
Margin Of Safety ◽  
New Formulation ◽  
Anaesthetic Effect

Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg–1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg–1, females; 75 mg kg–1, males) was combined with dexmedetomidine (0.05 mg kg–1). Finally, alfaxalone (20 mg kg–1, females; 60 mg kg–1, males) was combined with dexmedetomidine (0.05 mg kg–1) and fentanyl (0.1 mg kg–1). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.

Effect of Poly(D, L-lactic acid) Nanoparticles as Triptolide Carrier on Abating Rats Renal Toxicity by NMR-Based Metabolic Analysis

2008 ◽  
Vol 8 (7) ◽  
pp. 3493-3499 ◽  
Author(s):  
Mingxing Liu ◽  
Jing Dong ◽  
Yajiang Yang ◽  
Xiangliang Yang ◽  
Huibi Xu
Keyword(s):  
Lactic Acid ◽  
Renal Toxicity ◽  
Circulatory System ◽  
Renal Lesion ◽  
Sprague Dawley ◽  
H Nmr ◽  
Metabolic Analysis ◽  
Sprague Dawley Rats ◽  
New Formulation

The aim of this study is to investigate the effect of poly(D, L-lactic acid) (PLA) nanoparticles as triptolide carrier on abating renal toxicity for Sprague Dawley rats after oral administration. Triptolide has severe toxicities on digestive, urogenital and blood circulatory system. High-resolution 600-MHz 1H-nuclear magnetic resonance (1H-NMR)-based metabolic analysis was performed on urine samples obtained from five groups of Sprague Dawley rats administrated with free triptolide and triptolide-loaded PLA nanoparticles at day 5, 10 and 15. The relative concentrations of biomarkers for renal lesion caused by triptolide were determined by 1H-NMR. The disorder of metabolism was characterized by the exceptional changes of the relative concentrations of succinate, 2-oxoglutarate and citrate. Similarly, the renal lesion was characterized by an increase of the relative concentrations of trimethylamine N-oxide and dimethylglycine, and a decrease of that of urea and allantoin. These results revealed that triptolide-loaded PLA nanoparticles might abate the renal toxicity of triptolide in comparison with identical doses of the free drug. The higher the dose (0.6 mg/kg), the more pronounced was this trend during long-term application. These results were further confirmed by histopathological changes. These results indicated that PLA nanoparticles provided a promising new formulation to abate the renal toxicity caused by triptolide.

scholarly journals Systemic Administration of Tempol Attenuates the Cardiorespiratory Depressant Effects of Fentanyl

2021 ◽  
Vol 12 ◽  
Author(s):  
Santhosh Baby ◽  
Ryan Gruber ◽  
Joseph Discala ◽  
Veljko Puskovic ◽  
Nijo Jose ◽  
...  
Keyword(s):  
Minute Ventilation ◽  
Oxidant Stress ◽  
Sprague Dawley ◽  
Systemic Injection ◽  
Analgesic Effects ◽  
Opioid Receptor Agonist ◽  
Sprague Dawley Rats ◽  
Freely Moving ◽  
Dose Dependent ◽  
Prior Administration

Fentanyl is a high-potency opioid receptor agonist that elicits profound analgesia and suppression of breathing in humans and animals. To date, there is limited evidence as to whether changes in oxidant stress are important factors in any of the actions of acutely administered fentanyl. This study determined whether the clinically approved superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), or a potent antioxidant, N-acetyl-L-cysteine methyl ester (L-NACme), modify the cardiorespiratory and analgesic actions of fentanyl. We examined whether the prior systemic injection of Tempol or L-NACme affects the cardiorespiratory and/or analgesic responses elicited by the subsequent injection of fentanyl in isoflurane-anesthetized and/or freely moving male Sprague-Dawley rats. Bolus injections of Tempol (25, 50 or 100 mg/kg, IV) elicited minor increases in frequency of breathing, tidal volume and minute ventilation. The ventilatory-depressant effects of fentanyl (5 μg/kg, IV) given 15 min later were dose-dependently inhibited by prior injections of Tempol. Tempol elicited dose-dependent and transient hypotension that had (except for the highest dose) resolved when fentanyl was injected. The hypotensive responses elicited by fentanyl were markedly blunted after Tempol pretreatment. The analgesic actions of fentanyl (25 μg/kg, IV) were not affected by Tempol (100 mg/kg, IV). L-NACme did not modify any of the effects of fentanyl. We conclude that prior administration of Tempol attenuates the cardiorespiratory actions of fentanyl without affecting the analgesic effects of this potent opioid. As such, Tempol may not directly affect opioid-receptors that elicit the effects of fentanyl. Whether, the effects of Tempol are solely due to alterations in oxidative stress is in doubt since the powerful antioxidant, L-NACme, did not affect fentanyl-induced suppression of breathing.

Characterization of the antinociceptive effects of intrathecal DALDA peptides following bolus intrathecal delivery

2019 ◽  
Vol 19 (1) ◽  
pp. 193-206 ◽  
Author(s):  
Shinichi Kokubu ◽  
Kelly A. Eddinger ◽  
Thi M.-D. Nguyen ◽  
Lena Libertad Huerta-Esquivel ◽  
Shigeki Yamaguchi ◽  
...  
Keyword(s):  
Phase 1 ◽  
Intrinsic Activity ◽  
Treated Animal ◽  
Sprague Dawley ◽  
Cross Tolerance ◽  
Duration Of Action ◽  
Analgesic Effects ◽  
Thermal Escape ◽  
Sprague Dawley Rats ◽  
Antinociceptive Effects

Abstract Background and aims We systematically characterized the potency and side effect profile of a series of small opioid peptides with high affinity for the mu opioid receptor. Methods Male Sprague Dawley rats were prepared with intrathecal (IT) catheters, assessed with hind paw thermal escape and evaluated for side effects including Straub tail, truncal rigidity, and pinnae and corneal reflexes. In these studies, DMT-DALDA (dDAL) (H-Dmt-D-Arg-Phe-Lys-NH2 MW=981), dDALc (H-Dmt-Cit-Phe-Lys-NH2 MW=868), dDALcn (H-Dmt-D-Cit-Phe-Nle-NH2 MW=739), TAPP (H-Tyr-D-Ala-Phe-Phe-NH2 MW=659), dDAL-TICP ([Dmt1]DALDA-(CH2)2-NH-TICP[psi]; MW=1519), and dDAL-TIPP (H-Dmt-D-Arg-Phe-Lys(Nε-TIPP)-NH2 were examined. In separate studies, the effects of approximately equiactive doses of IT DMT DALDA (10 pmol), morphine (30 nmol) and fentanyl (1 nmol) were examined on formalin-induced flinching at different pretreatment intervals (15 min – 24 h). Results (1) All agents resulted in a dose-dependent reversible effect upon motor function (Straub Tail>Truncal rigidity). (2) The ordering of analgesic activity (%MPE) at the highest dose lacking reliable motor signs after bolus delivery was: DMT-DALDA (80%±6/3 pmol); dDALc (75%±8/1 pmol); dDALcn (84%±10/300 pmol); TAPP (56%±12/10 nmol); dDAL-TICP (52%±27/300 pmol). (3) All analgesic effects were reversed by systemic (IP) naloxone (1 mg/kg). Naltrindole (3 mg/kg, IP) had no significant effect upon the maximum usable peptide dose. (4) Tolerance and cross-tolerance development after 5 daily boluses of DMT-DALDA (3 pmol) and morphine (30 nmol) revealed that both agents displayed a progressive decline over 5 days. (5) Cross-tolerance assessed at day 5 revealed a reduction in response to morphine in DMT-DALDA treated animal but not DMT-DALDA in the morphine treated animal, indicating an asymmetric cross-tolerance. (6) IT DMT-DALDA, morphine and fentanyl resulted in significant reductions in phase 1 and phase 2 flinching. With a 15 min pretreatment all drugs resulted in comparable reductions in flinching. However, at 6 h, the reduction in flinching after DMT-DALDA and morphine were comparably reduced while fentanyl was not different from vehicle. All effects on flinching were lost by 24 h. Conclusions These results emphasize the potent mu agonist properties of the DALDA peptidic structure series, their persistence similar to morphine and their propensity to produce tolerance. The asymmetric cross-tolerance between equiactive doses may reflect the relative intrinsic activity of morphine and DMT-DALDA. Implications These results suggest that the DALDA peptides with their potency and duration of action after intrathecal delivery suggest their potential utility for their further development as a spinal therapeutic to manage pain.

scholarly journals Profiling the Effects of Repetitive Morphine Administration on Motor Behavior in Rats

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4355
Author(s):  
Alok K. Paul ◽  
Nuri Gueven ◽  
Nikolas Dietis
Keyword(s):  
Motor Behavior ◽  
Tail Flick ◽  
High Dose ◽  
Behavioral Tolerance ◽  
Sprague Dawley ◽  
Analgesic Tolerance ◽  
Morphine Dose ◽  
Analgesic Effects ◽  
Sprague Dawley Rats ◽  
Morphine Administration

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levels of analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing on non-analgesic effects has been overlooked. This study aimed to characterize morphine-induced behavior and the development and progression of morphine-induced behavioral tolerance. Adult male Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in two dose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day). Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in an open-field arena, before and 30 min post-injections. Antinociception was measured using tail-flick and hot-plate assays. All measured parameters were highly suppressed in both dosing groups on the first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatment progressed. Animals in the high-dose group showed increased locomotor activity after 10 days of morphine treatment. This excitatory phase converted to an inhibition of behavior when a higher morphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high-dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.

scholarly journals Comparing the Rat Grimace Scale and a composite behaviour score in rats

2018 ◽  
Author(s):  
Cassandra Klune ◽  
Amy Larkin ◽  
Vivian Leung ◽  
Daniel SJ Pang
Keyword(s):  
Saline Group ◽  
Laboratory Animals ◽  
Similar Degree ◽  
Sprague Dawley ◽  
Analgesic Effects ◽  
Sprague Dawley Rats ◽  
Pain Scales ◽  
Postural Changes ◽  
Behaviour Score ◽  
To Receive

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram reliant on postural changes), are both promising pain assessment methods. Both scales have been used to assess pain in a laparotomy model, however, they have never been compared directly and the knowledge of how different analgesics may affect these two scales is limited. This study aimed to provide a comparison to discriminate the temporal and analgesic response in a laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block randomized to receive saline, meloxicam (2 mg/kg) or buprenorphine (0.05 mg/kg) 30 minutes before a laparotomy model. Rats were video-recorded before surgery (BL) and at 30, 150, 270, and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, blinded observer. Both CBS and RGS scores increased significantly at all post surgical timepoints in the saline group. Post-surgical CBS scores did not increase significantly above baseline levels in the groups given meloxicam or buprenorphine. However, the RGS scores only remained low in the buprenorphine group while scores increased significantly in the meloxicam group, to a similar degree as in the saline group. These findings suggest that the CBS is more sensitive to the analgesic effects of NSAIDs than the RGS.

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.

scholarly journals Histopathological and analgesic effects of intrathecal dexmedetomidine, racemic ketamine, and magnesium sulfate in rats

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Erhan Ozyurt ◽  
Zekiye Bigat ◽  
Bilge Karsli ◽  
Arda Tasatargil ◽  
Inanc Elif Gurer ◽  
...  
Keyword(s):  
Magnesium Sulfate ◽  
Control Group ◽  
Sprague Dawley ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Analgesic Effects ◽  
Sprague Dawley Rats ◽  
Racemic Ketamine ◽  
Preservative Free

Abstract Background This study aims to investigate the histopathological and analgesic effects of intrathecal administration of dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate in Sprague Dawley rats. This study included 40 male Sprague Dawley rats weighing between 240 and 260 g. After the intrathecal catheterization, the rats were randomly divided into four groups. Following the baseline measurements, no drugs were administered in the control group (group C). Simultaneously, 0.02 ml (1 μgr/kg) of dexmedetomidine was administered in group D, 0.02 ml (1 mg/kg) preservative-free racemic ketamine in group K and 0.02 ml (0.05 mg/kg) magnesium sulfate in group M via intrathecal route. Concomitantly, the hot-plate test was used to measure the analgesic effect of drugs. For histopathological evaluation, the rats were sacrificed to obtain the medulla spinalis. Results The hot-plate test revealed that the mean response time was 6.3 ± 1.2 s in baseline measurements without medication. However, prolongation in the mean response times of the drug-administered groups to the hot-plate test was also observed. Upon histopathological examination, myelin degeneration was detected in all study groups. No inflammation was observed in rats in group D, whereas inflammation was noted in only two rats in group K. Concerning the presence of red neurons, the only group that differed from the control group belonged to group K. Conclusions Dexmedetomidine, preservative-free racemic ketamine, and magnesium sulfate have an analgesic effect when administered intrathecally in rats. Of these drugs, preservative-free racemic ketamine stands out as the most histopathologically safe drug.

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

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