Involvement of Noradrenergic Neurotransmission in the Stress- but not Cocaine-Induced Reinstatement of Extinguished Cocaine-Induced Conditioned Place Preference in Mice: Role for β-2 Adrenergic Receptors

The responsiveness of central noradrenergic systems to stressors and cocaine poses norepinephrine as a potential common mechanism through which drug re-exposure and stressful stimuli promote relapse. This study investigated the role of noradrenergic systems in the reinstatement of extinguished cocaine-induced conditioned place preference by cocaine and stress in male C57BL/6 mice. Cocaine- (15 mg/kg, i.p.) induced conditioned place preference was extinguished by repeated exposure to the apparatus in the absence of drug and reestablished by a cocaine challenge (15 mg/kg), exposure to a stressor (6-min forced swim (FS); 20–25°C water), or administration of the α-2 adrenergic receptor (AR) antagonists yohimbine (2 mg/kg, i.p.) or BRL44408 (5, 10 mg/kg, i.p.). To investigate the role of ARs, mice were administered the nonselective β-AR antagonist, propranolol (5, 10 mg/kg, i.p.), the α-1 AR antagonist, prazosin (1, 2 mg/kg, i.p.), or the α-2 AR agonist, clonidine (0.03, 0.3 mg/kg, i.p.) before reinstatement testing. Clonidine, prazosin, and propranolol failed to block cocaine-induced reinstatement. The low (0.03 mg/kg) but not high (0.3 mg/kg) clonidine dose fully blocked FS-induced reinstatement but not reinstatement by yohimbine. Propranolol, but not prazosin, blocked reinstatement by both yohimbine and FS, suggesting the involvement of β-ARs. The β-2 AR antagonist ICI-118551 (1 mg/kg, i.p.), but not the β-1 AR antagonist betaxolol (10 mg/kg, i.p.), also blocked FS-induced reinstatement. These findings suggest that stress-induced reinstatement requires noradrenergic signaling through β-2 ARs and that cocaine-induced reinstatement does not require AR activation, even though stimulation of central noradrenergic neurotransmission is sufficient to reinstate

The Medical School to Residency Transition: Examining Program Directors' Expectations and Perspectives

Purpose Residency program directors (PDs) identify that students are unprepared for the patient care responsibilities expected of them upon entering residency. The Association for American Medical Colleges (AAMC) developed the Core Entrustable Professional Activities (Core EPAs) for Entering Residency to address this concern by defining thirteen core tasks students should be able to do with minimal supervision upon graduation. A subsequent learner handover aims to smooth the transition from undergraduate (UME) to graduate medical education (GME). We aimed: 1 - To identify observable practice activities, defining what PDs expect of entering interns based on the implementation of the Core EPAs.  2 - To explore program directors’ (PDs) perspective of the learner handover from UME to GME.   Method Using Delphi consensus methodology, twelve expert medical educators in EM drafted observable practice activities (OPAs) based on the Core EPAs and their associated core functions. Twelve EM PDs participated in three rounds of voting with consensus for inclusion set at 70%. Thematic analysis of comments supporting votes was performed using an inductive approach.  Using case study methodology, semi-structured interviews were conducted with 12 Emergency medicine PDs. Participants were asked to describe their current perception of the learner handover from UME to GME. Thematic analysis was performed of these interviews using an inductive approach.   Results 321 OPAs were drafted and 127 were adopted as expectations for entering interns based on the Core EPAs. The adopted OPAs were all general expectations; none were specialty-specific. Four main themes emerged from the comments: Schools are not responsible for specialty-specific training, PDs do not trust schools’ assessments, supervision expectations of graduates should be lowered for higher-order EPAs, and the context in which the student performs a task and its associated complexity matter greatly in entrustment decisions.  Two main themes emerged from the case study: The invisibility of the learner handover and the challenges of creating a successful UME-to-GME learner handover. PDs described the current state of the learner handover as “nonexistent,” while also acknowledging that certain information is transmitted from UME to GME particularly as part of the residency selection process. Participants also highlighted key challenges to successful learner handover from UME to GME which centered around conflicting purposes and expectations of UME and GME, issues of trust and transparency between UME and GME stakeholders, and the scarcity of assessment data to hand over.  Discussion PDs agree regarding many basic expectations set forth by the Core EPAs; however, they also feel that specialty training should be left to residency programs and feel the need to verify entrustment within their context. Additionally, challenges with the learner handover may require shifting the culture of trust, transparency, and communication between UME and GME stakeholders particularly around assessment and summative entrustment processes. National level organizations may need to examine this process and come to consensus on a unified approach to the transmission of transparent, growth-oriented learner data as part of a formal learner handover from UME to GME