Effect of Subcutaneous Injection and Oral Voluntary Ingestion of Buprenorphine on Post-Operative Serum Corticosterone Levels in Male Rats

Abstract

Background: Adequate peri-operative analgesia may reduce post-operative stress response and improve recovery in laboratory animals. We have established a method involving repeated automated blood sampling, allowing quantification of serum corticosterone levels in rats for stress assessment without stress-inducing handling or restraint. In the present study, the effects of the commonly used route of buprenorphine administration (0.05 mg/kg injected subcutaneously) were compared with oral administration (0.4 mg/kg mixed with Nutella® and orally administered by voluntary ingestion) in male Sprague-Dawley rats. Methods: A catheter was placed in the jugular vein and attached to an Accusampler® for automated blood sampling. During 96 h after surgery, blood was collected at specified time points. Pre- and post-operative body weights and water consumption were registered. Results: Buprenorphine significantly suppressed levels of circulating corticosterone after the oral but not after the subcutaneous treatment. Both buprenorphine treatments had a positive impact on maintenance of body weight and water consumption, compared to the control group that received no buprenorphine. Conclusion: The present investigation suggests that oral voluntary ingestion ad libitum is an efficacious, convenient and non-invasive way of administering peri-operative buprenorphine to rats, as judged by corticosteroid response and effects on body weight and water consumption.

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

“…A recent study demonstrated that group-housed animals transferred to another location and then separated to single housing did not exhibit any significant stress response after two days that could be measured by the quantification of corticosterone excreted in faeces. 22 The present study demonstrated that the method for oral buprenorphine administration that we previously found to be effective in Sprague-Dawley rats, 12 results in a similar corticosterone profile and body weight change in Wistar rats. Both stocks are among the most commonly used laboratory rats, due to their high vigour and reproductive ability and their docility.…”

“…15 Group sizes were determined using a power analysis as described in the literature, 18,19 based on data from previous investigation where corticosterone levels in blood have been investigated. 12,17 Treatments were administered according to a randomized block design sorted by stock.…”

“…Thereafter, blood was collected after 2, 6, 10, 14 and 18 h, followed by a sample collected at 12:00 and 00:00 h until 96 h after surgery. The rationale for treating the animals for such a long period of time, despite the relatively minor surgical procedure, was to monitor the return to basal circadian rhythmicity of corticosterone, similar to a previous study, 12 and investigate possible stock-related differences. In total, 13 samples of 150 mL each were collected from the rats, corresponding to a blood withdrawal of approximately 0.5% of the animals' body weight during the whole experiment.…”

“…12 -17 Recently, we investigated the postoperative effects of pre-emptive buprenorphine on the corticoid system, both after SC injection and after voluntary ingestion (VI), and found that buprenorphine after VI administration was able to reduce the corticosterone levels in the circulation during 18 h after surgery in Sprague-Dawley rats. 12 In addition, the oral administration resulted in beneficial effects on postoperative body weight gain, equal to the effects after SC administration.…”

“…This type of administration has been found to improve postoperative recovery. 11,12 Corticosterone is generally considered as a relevant marker for acute stress, and several studies have demonstrated the usefulness of quantifying plasma corticosterone or faecal excretion of corticosterone and corticosterone metabolites for the assessment of surgical and postoperative stress. 12 -17 Recently, we investigated the postoperative effects of pre-emptive buprenorphine on the corticoid system, both after SC injection and after voluntary ingestion (VI), and found that buprenorphine after VI administration was able to reduce the corticosterone levels in the circulation during 18 h after surgery in Sprague-Dawley rats.…”