Withdrawal from psychostimulants increases anxiety states, and amphetamine-treated rats show increased CRF2 receptors in the serotonergic cell body region, the dorsal raphe nucleus (dRN). In the current study, amphetamine (2.5 mg/kg, ip, 14 days) pre-treated rats spent less time in open arms of the elevated plus maze compared saline pre-treated rats at both 24 hours or 2 weeks of withdrawal, and CRF2 receptor antagonism (ASV-30; 2 μg/0.5 μl) within the dRN reversed the effects of amphetamine withdrawal on anxiety-like behavior. Overall, results suggest that CRF2 receptor antagonism may be a novel pharmacological target for anxiety states during drug withdrawal.

Social isolation of rats during the early part of development increases social anxiety-like behavior in adulthood. Furthermore, early-life social isolation increases the levels of corticotropin-releasing factor (CRF) receptors in the serotonergic dorsal raphe nucleus (dRN) of adult rats. Interactions between serotonin and CRF systems are thought to mediate anxiety behavior. Therefore, we investigated the effects of CRF receptor antagonism within the dRN on social anxiety-like behavior after early-life social isolation. Male rats were reared in isolation or in groups from weaning until midadolescence, and rehoused in groups and allowed to develop into adulthood. Adult rats underwent surgery to implant a drug cannula into the dRN. After recovery from surgery and acclimation to the testing arena, rats were infused with vehicle or the CRF receptor antagonist D-Phe-CRF (12-41) (50 or 500 ng) into the dRN before a social interaction test. Isolation-reared rats pretreated with vehicle exhibited increased social anxiety-like behavior compared with rats reared in groups. Pretreatment of the dRN with D-Phe-CRF (12-41) significantly reduced social anxietylike behaviors exhibited by isolation-reared rats. Overall, this study shows that early-life social stress results in heightened social anxiety-like behavior, which is reversed by CRF antagonism within the dRN. These data suggest that CRF receptor antagonists could provide a potential treatment of stress-related social anxiety.

Background: This study aimed to investigate if nonsteroidal anti-inflammatory drugs (NSAIDs) used in the acute phase of bone healing in children with fractures result in delayed union or nonunion as compared with patients who do not take NSAIDs for pain control during this same time period. Methods: In this prospective, randomized, parallel, single-blinded study, skeletally immature patients with long bone fractures were randomized to 1 of 2 groups for their postfracture pain management. The NSAID group was prescribed weight-based ibuprofen, whereas the control group was not allowed any NSAID medication and instead prescribed weight-based acetaminophen. Both groups were allowed to use oxycodone for breakthrough pain. The primary outcome was fracture healing assessed at 2, 6, and 10 weeks. Results: One-hundred-two patients were enrolled between February 6, 2014 and September 23, 2016. Ninety-five patients (with 97 fractures) completed a 6-month follow-up (46 patients with 47 fractures in the control group and 49 patients 50 fractures in the NSAID group). None achieved healing at 1 to 2 weeks. By 6 weeks, 37 of 45 patients (82%) of control group and 46 out of 50 patients (92%) of ibuprofen group had healed fractures (P=0.22). At 10 to 12 week follow-up, 46 (98%) of the control group fractures were healed and 50 (100%) of the ibuprofen group fractures were healed. All were healed by 6 months. Healing was documented at a mean of 40 days in the control group and 31 days in the ibuprofen group (P=0.76). The mean number of days breakthrough oxycodone was used was 2.4 days in the control group and 1.9 days in the NSAID group (P=0.48). Conclusion: Ibuprofen is an effective medication for fracture pain in children and its use does not impair clinical or radiographic long bone fracture healing in skeletally immature patients. Level of Evidence: Level I—therapeutic.