Lack of analgesic efficacy in female rats of the commonly recommended oral dose of buprenorphine.

Previous work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective as the standard therapeutic subcutaneous dose for postoperative analgesia in male Long-Evans (hooded) and Sprague-Dawley (albino) rats. The aim of the current study was to extend this analysis to female rats. We measured the pain threshold in adult female rats in diestrus or proestrus before and 30 and 60 min after oral buprenorphine (0.5 mg/kg,), the standard subcutaneous dose of buprenorphine (0.05 mg/kg), or vehicle only (1 ml/kg each orally and subcutaneously). Female rats showed an increased pain threshold (analgesia) after subcutaneous buprenorphine but no change in pain threshold after either oral buprenorphine or vehicle only. Estrous cycle stage (proestrus versus diestrus) did not affect the analgesic effects of buprenorphine, but rats in proestrus showed significantly lower pain thresholds (less tolerance to pain) than did those in diestrus. These results show that the oral dose of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia in female rats and therefore is not as effective as the standard subcutaneous dose.

Ketamine-xylazine-acepromazine anesthesia and postoperative recovery in rats.

We evaluated the effect of ketamine-xylazine-acepromazine anesthesia (31.25, 6.25, and 1.25 mg/kg subcutaneously, respectively) on postsurgical recovery in male Sprague-Dawley (Crl:SD) rats undergoing laparotomy with and without the postoperative analgesic ketorolac. Recovery was determined by changes in body weight (BW) and water intake. The time of ketorolac administration (5 mg/kg intramuscularly), 60 min after anesthetic injection, was based on return of the pedal withdrawal reflex in Long-Evans (HsdBlu:LE) rats undergoing stereotaxic surgery in a separate experiment. Results were compared with those of housing and anesthesia controls as well as of laparotomized rats receiving a single sugared treat for nonpharmacologic management of postoperative pain. Surgery took place on day 0; the first 24 h postsurgery was considered the "acute phase," and days 1 through 4 comprised the "recovery phase." Results suggest that 1) the anesthetic mixture is fast- and long-acting and provides sufficient immobility, loss of consciousness, and analgesia; 2) during the acute phase, rats subjected to laparotomy did not lose more BW than rats exposed to anesthesia alone; 3) water intake during both phases did not significantly differ between treatment groups; 4) postsurgical ketorolac administration did not minimize BW loss during the acute phase nor cause any adverse effects under this anesthetic regimen; and 5) provision of single sugared treats had salutary effects on BW recovery. This finding suggests that postsurgical BW loss after use of this anesthetic mixture is due to distress unrelated to pain; this nonpain distress may have masked potential beneficial effects of ketorolac.

Sex differences in the discriminative stimulus effects of m-chlorophenylpiperazine and ethanol withdrawal.

RATIONALE: The serotonergic system plays a role in regulation of anxiety and ethanol withdrawal (EW). Nevertheless, few studies have assessed sex differences in serotonergic effects on EW. OBJECTIVES: This study examined sex differences in the anxiogenic stimuli induced by a serotonin (5-HT)(1b,2) agonist, meta-chlorophenylpiperazine (mCPP), prior to ethanol and during EW. METHODS: Gonadectomized or sham-operated adult male and female rats and 17beta-estradiol (2.5 mg, 21-day release, s.c.) -replaced ovariectomized (OVX) rats were trained to discriminate mCPP (1.2 mg/kg, i.p.) from saline in a two-lever choice task for food. Latency to the first lever press and mCPP lever selection were measured following mCPP (0-1.2 mg/kg). Rats then received chronic ethanol-containing liquid diet (6.5%) for 10 days and were tested for mCPP lever selection 12 h and 36 h after removal of ethanol. RESULTS: Fewer sham female and beta-estradiol-replaced OVX rats selected the mCPP lever than male or OVX rats, and showed an increased initiation latency after mCPP injection. During EW (12 h and 36 h), fewer sham female and beta-estradiol-replaced OVX rats responded on the mCPP-lever after saline injection as well as after mCPP challenge than male or OVX rats. Castration did not alter any response of male rats to mCPP. CONCLUSIONS: (1) mCPP discrimination is a useful measure of EW in male and female rats; and (2) sham female and beta-estradiol-replaced OVX rats are less sensitive to the discriminative stimulus prior to and during EW, but more sensitive to impaired behavioral initiation induced by mCPP than male or OVX rats.