Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice

Abelson, Klas S P; Jacobsen, Katja Kemp; Sundbom, Renée; Kalliokoski, Otto; Hau, Jann

doi:10.1258/la.2012.012028

Cited by 55 publications

(43 citation statements)

References 7 publications

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“…An analgesic regimen, consisting of 1 mg/kg body weight (BW) buprenorphine (Temgesic; Schering-Plough Europe, Brussels, Belgium) was given in nut paste (Nutella®, Ferrero, Pino Torinese, Italy) for voluntary ingestion prior to surgery and then once daily for two days post-surgery, as described previously [21,22]. To ensure adequate pre-emptive analgesia, the mice were injected with 0.1 mg buprenorphine/ kg BW before being brought out of anesthesia.…”

Section: Methodsmentioning

confidence: 99%

Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

et al. 2016

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Automated blood sampling through a vascular catheter is a frequently utilized technique in laboratory mice. The potential immunological and physiological implications associated with this technique have, however, not been investigated in detail. The present study compared plasma levels of the cytokines IL-1β, IL-2, IL-6, IL-10, IL-17A, GM-CSF, IFN-γ and TNF-α in male NMRI mice that had been subjected to carotid artery catheterization and subsequent automated blood sampling with age-matched control mice. Body weight and histopathological changes in the surgical area, including the salivary glands, the heart, brain, spleen, liver, kidneys and lungs were compared. Catheterized mice had higher levels of IL-6 than did control mice, but other cytokine levels did not differ between the groups. No significant difference in body weight was found. The histology revealed inflammatory and regenerative (healing) changes at surgical sites of all catheterized mice, with mild inflammatory changes extending into the salivary glands. Several catheterized mice had multifocal degenerative to necrotic changes with inflammation in the heart, kidneys and livers, suggesting that thrombi had detached from the catheter tip and embolized to distant sites. Thus, catheterization and subsequent automated blood sampling may have physiological impact. Possible confounding effects of visceral damage should be assessed and considered, when using catheterized mouse models.

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Section: Methodsmentioning

confidence: 99%

Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

et al. 2016

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“…The voluntary consumption of an acute poison is both a novel and realistic model for mass-poisoning scenarios. Much of the literature that uses voluntary consumption falls into one of several types: chronic low-level exposures (e.g., [39]), descriptions and analyses of events that previously occurred (e.g., [40, 41]), masking/delivering medicinal doses (e.g., [42–44]), or delivering a substance that has reinforcing properties on its own, such as ethanol or morphine [45–48]. There is a severe lack of information regarding the oral consumption of acute poisons, despite the fact that many chemicals are oral hazards.…”

Section: Discussionmentioning

confidence: 99%

Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery

et al. 2017

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Tetramethylenedisulfotetramine (tetramine, or TETS) is a highly toxic rodenticide that has been responsible for over 14,000 accidental and intentional poisonings worldwide. Although the vast majority of TETS poisonings involved tainted food or drink, the laboratory in vivo studies of TETS intoxication used intraperitoneal injection or gavage for TETS exposure. Seeking to develop and characterize a more realistic model of TETS intoxication in the present study, rats were trained to rapidly and voluntarily consume a poisoned food morsel. Initially, the overt toxic effects of TETS consumption across a large range of doses were characterized, then a focused range of doses was selected for more intensive behavioral evaluation (in operant test chambers providing a variable-interval schedule of food reinforcement). The onset of intoxication following voluntary oral consumption of TETS was rapid, and clear dose-dependent response-rate suppression was observed across multiple performance measures within the operant-chamber environment. At most doses, recovery of operant performance did not occur within 30 hours. Food consumption and body weight changes were also dose dependent and corroborated the behavioral measures of intoxication. This voluntary oral-poisoning method with concomitant operant-behavioral assessment shows promise for future studies of TETS (and other toxic chemicals of interest) and may be extremely valuable in characterizing treatment outcomes.

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“…Bupenorphine can be administered subcutaneously or orally in rats and mice (Liles and Flecknell, 1992a, Volker et al, 2000, Abelson et al, 2012 and has shown to be effective in treating multiple pain conditions including neuropathic pain (Guarnieri et al, 2012). Preanaesthetic subcutaneous (SC) administration of buprenorphine, during ketamine-medetomidine injectable anaesthesia, was associated with respiratory arrest and mortality in rats (Hedenqvist et al, 2000).…”

Section: Buprenorphine Is the Most Commonly Used Rodent Analgesic Agentmentioning

confidence: 99%

The safety, efficacy and neuromotor effects of the neurosteroid anaesthetic alfaxalone in rats

Lau¹

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Rodents are routinely anaesthetised for husbandry and biomedical research purposes. All anaesthetics carry a degree of risk, complications and side effects. An ideal anaesthetic for rodents is safe, predictable, alleviates pain and distress and can be performed without specialist training. A survey was created to identify anaesthetic agents frequently administered to rodents currently utilised by the research community. Findings indicated injectable anaesthetics were very commonly used and complications were often associated with use, highlighting the lack of a safe, predictable laboratory rodent anaesthetic protocol.Alfaxalone is a neuroactive steroid injectable anaesthetic agent with a high margin of safety, and is commonly used in veterinary anaesthesia as the Alfaxan® formulation. I sought to establish whether alfaxalone could be used as an injectable anaesthetic agent for laboratory rodents. A plasma pharmacokinetics study was performed using IV and IP Alfaxan® in adult female Wistar rats (7-10 weeks). Mean T 1/2elim for 2 and 5 mg.kg -1 IV was short (~17 minutes), but could not be estimated for IP dosing due to sustained plasma levels for up to 60 minutes after injection. Cl p for IV injection was calculated at 24.5% and 23% of cardiac output respectively. The observed C max was 2.99 mg.L -1 for IP administration, and 2.2 ± 0.9 and 5.2 ± 1.3 mg.L -1 for 2 and 5 mg.kg -1 IV administration respectively. AUC 0-60 was 96 min.mg.L -1 for IP dosing. The relative bioavailability for IP dosing was 26% and 28%, compared to IV doses of 2 and 5mg.kg -1 respectively. Alfaxalone given IP caused longer sleep times than IV dosing, although anaesthesia was not induced in 30% of rats.Importantly, all rats exhibited muscle twitching after alfaxalone administration. I then sought to test whether combining IP injection of Alfaxalone with common premedication agents could improve anaesthetic induction rates and reduce muscle twitching, to provide a viable anaesthetic regimen for rats. Medetomidine (0.5 mg.kg -1 ), medetomidine-butorphanol (0.35 mg.kg -1 -0.2 mg.kg -1 ), Acetylpromazine (ACP) -methadone (3 mg.kg -1 -0.7 mg.kg -1 ) and ACP-xylazine (3 mg.kg -1 -3 mg.kg -1 )were administered IP 10 minutes prior to IP alfaxalone (20 mg.kg -1 ). ACP-xylazine, medetomidine and medetomidine-butorphanol all significantly reduced twitching. Medetomidine-butorphanol provided surgical anaesthesia without prolonged recovery and provided an adequate plane of anaesthesia for short painful surgical procedures.However, none of these premedication agents fully eliminated alfaxalone-induced muscle twitching. I therefore carried out electrophysiological studies of motor neurons (MN), to determine the mechanism causing neuromotor excitation in response to alfaxalone. Previous data has shown that alfaxalone can modulate strychnine-sensitive glycinergic receptors, which may, in part, contribute to the adverse neuromotor excitatory responses manifested as muscle twitching during alfaxalone anaesthesia. The 3 effects of alfaxalone on inhibito...

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Voluntary ingestion of nut paste for administration of buprenorphine in rats and mice

Cited by 55 publications

References 7 publications

Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

Carotid Catheterization and Automated Blood Sampling Induce Systemic IL-6 Secretion and Local Tissue Damage and Inflammation in the Heart, Kidneys, Liver and Salivary Glands in NMRI Mice

Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery

The safety, efficacy and neuromotor effects of the neurosteroid anaesthetic alfaxalone in rats

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