Plasma concentrations of corticosterone and buprenorphine in rats subjected to jugular vein catheterization

Abstract

The present study investigated the postoperative plasma concentrations of corticosterone and buprenorphine in male Wistar and Sprague-Dawley rats, treated with buprenorphine administered either through subcutaneous (SC) injection or through voluntary ingestion (VI). The animals were treated with buprenorphine for pre-emptive analgesia prior to surgical placement of a jugular catheter, followed by automated blood sampling during 96 h. Buprenorphine was administered on a regular basis throughout the experiment, and blood was collected on selected time points. Body weight was measured before and 96 h after surgery. It was found that the two rat stocks responded in a similar manner to both buprenorphine treatments, with the exception of body weight change in Wistar rats, in which body weight was reduced after SC treatment. The plasma concentration of corticosterone was significantly higher in the SC-treated animals than in the VI-treated animals during the first 18 h of the study, while plasma buprenorphine concentration was at least as high and more even over time after VI treatment. The present study shows that buprenorphine administration through VI is suitable for both Wistar and Sprague-Dawley rats, with lower stress response and higher plasma concentrations of buprenorphine than after the traditional SC route of administration.

Side effects of pain and analgesia in animal experimentation

“…Voluntary oral administration of analgesia is another promising approach that avoids the negative effects of handling. Several routes of oral administration have been described, such as mixing analgesics with flavored gelatine 21 , Nutella 22 , regular diet 23 or drinking water 24 . These studies in mice and rats have shown that several analgesics are efficient when administered orally and voluntarily.…”

Buprenorphine via drinking water and combined oral-injection protocols for pain relief in mice

“…Despite these concerns, several studies in mice and rats have shown that buprenorphine has sufficient analgesic efficacy when administered orally. Several routes of oral administration have been described, such as mixing buprenorphine with flavored gelatin (Liles, Flecknell et al 1998), Nutella ® (Goldkuhl, Jacobsen et al 2010, Kalliokoski, Jacobsen et al 2011, gel delivery systems (Hovard, Teilmann et al 2015) or with the regular diet of the mice (MolinaCimadevila, Segura et al 2014). …”

“…For instance, food neophobia is a well-known obstacle in the oral administration of analgesics in mice. Habituation to new food items is necessary in order to ensure sufficient intake and resulting therapeutic drug levels (Liles, Flecknell et al 1998, Goldkuhl, Jacobsen et al 2010, Kalliokoski, Jacobsen et al 2011, Hovard, Teilmann et al 2015. Moreover, even after habituation, the latency to ingestion of the drug, as well as the total amount ingested by the animals, might be difficult to anticipate (Hovard, Teilmann et al 2015).…”

“…Providing buprenorphine mixed with the regular diet might overcome the problem of food neophobia, as stated by Molina-Cimadevila et al (Molina-Cimadevila, Segura et al 2014). Nonetheless, medicated food items need to be prepared prior to administration, which might be costly and time consuming depending on the chosen food medium (Liles, Flecknell et al 1998, Goldkuhl, Jacobsen et al 2010, Kalliokoski, Jacobsen et al 2011, Hovard, Teilmann et al 2015. Alternatively, providing analgesia mixed with drinking water is a promising route of administration (Hayes, Raucci et al 2000, Jessen, Christensen et al 2007) since tap water is readily available at every facility and mixtures can be prepared within minutes.…”

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

“…Several studies have shown that buprenorphine administered in a sticky nut paste (Nutella w ), voluntarily ingested by laboratory rats and mice, is an effective analgesic strategy, with reduced stress and lower corticosterone levels in blood and faeces 4 -8 , and higher and prolonged buprenorphine concentrations in serum, when compared with traditional parenteral administration regimens 6,9 . However, this method is discouraged in some institutions, which is probably due to a lack of detailed instructions on how to apply the method, and uncertainty about how different animal models are affected by opioids.…”