Self-administration of methohexital, midazolam and ethanol: effects on the pituitary–adrenal axis in rhesus monkeys

There is disagreement in the literature with respect to how drugs of abuse affect the functioning of the hypothalamic–pituitary–adrenal (HPA) axis, and whether these changes in endocrine function may be related to the rewarding effects of these drugs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46363/1/213_2004_Article_1986.pd

The oxytocin analogue carbetocin prevents emotional impairment and stress-induced reinstatement of opioid-seeking in morphine-abstinent mice.

The main challenge in treating opioid addicts is to maintain abstinence due to the affective consequences associated with withdrawal which may trigger relapse. Emerging evidence suggests a role of the neurohypophysial peptide oxytocin (OT) in the modulation of mood disorders as well as drug addiction. However, its involvement in the emotional consequences of drug abstinence remains unclear. We investigated the effect of 7-day opioid abstinence on the oxytocinergic system and assessed the effect of the OT analogue carbetocin (CBT) on the emotional consequences of opioid abstinence, as well as relapse. Male C57BL/6J mice were treated with a chronic escalating-dose morphine regimen (20-100 mg/kg/day, i.p.). Seven days withdrawal from this administration paradigm induced a decrease of hypothalamic OT levels and a concomitant increase of oxytocin receptor (OTR) binding in the lateral septum and amygdala. Although no physical withdrawal symptoms or alterations in the plasma corticosterone levels were observed after 7 days of abstinence, mice exhibited increased anxiety-like and depressive-like behaviors and impaired sociability. CBT (6.4 mg/kg, i.p.) attenuated the observed negative emotional consequences of opioid withdrawal. Furthermore, in the conditioned place preference paradigm with 10 mg/kg morphine conditioning, CBT (6.4 mg/kg, i.p.) was able to prevent the stress-induced reinstatement to morphine-seeking following extinction. Overall, our results suggest that alterations of the oxytocinergic system contribute to the mechanisms underlying anxiety, depression, and social deficits observed during opioid abstinence. This study also highlights the oxytocinergic system as a target for developing pharmacotherapy for the treatment of emotional impairment associated with abstinence and thereby prevention of relapse

The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats

Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic–pituitary–adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46365/1/213_2005_Article_2164.pd

Emergency department utilisation by patients with a diagnosis of borderline personality disorder: An acute response to a chronic disorder.

OBJECTIVE: Patients with borderline personality disorder (BPD) are likely to attend the ED while experiencing crises and associated self-injury and suicidality. Our study describes the prevalence, features, and outcomes associated with ED presentations by patients diagnosed with BPD in Outer Eastern Melbourne, Australia. METHODS: A retrospective electronic audit of 157 364 ED attendances identified 700 unique BPD-related ED presentations between May 2015 and April 2016. For the purpose of comparison, 583 (81% female) of these 700 cases were matched with 'depression only' cases. ED re-presentation data were also extracted. RESULTS: The 583 matched BPD patients attended ED a total of 2807 times during the audit year compared with 1092 attendances for matched depression-only patients. BPD patients were more likely to: arrive by ambulance (50%); have comorbid substance abuse (44%); have a psychotic (15%) or bipolar disorder (17%); be under the care of a psychiatrist (31%); be case-managed (42%); and be admitted to an inpatient unit (21%). ED doctors saw 38% of BPD or depression patients within the recommended time according to their triage category. The majority (73%) of BPD patients attended ED more than once during the audit year (average 4.81 ± 6.63 times; range 2-78). CONCLUSION: Repeated ED attendance of a subset of patients diagnosed with BPD highlights both the severity of their presentation and the inadequacy of community mental health services for meeting their complex needs. Development of effective ED referral pathways with follow-up to engage patients in BPD-appropriate treatment will reduce the likelihood of crises and reliance on hospital EDs for acute episodic care