Evaluating the feasibility of implementing a prescription drug misuse prevention intervention in the community: a mixed methods study.

BACKGROUND: This study is part of a state-wide effort to promote the safe disposal of prescription medications and mitigate prescription drug misuse. The objective of this study was to evaluate the implementation of a two-component prevention intervention through Community Prevention Organizations (CPOs) in Texas. The first component involved the distribution of in-home disposal products (IHDP) and the second focused on providing education of the risks of prescription drug misuse. METHODS: This study followed a mixed methods sequential explanatory study design. In the quantitative phase, the extent to which CPOs carried out the intervention was determined by the distribution rate - a proportion representing the number of IHDP distributed to end users from the amount of IHDP the CPO was shipped. This measure was used to organize the CPOs in to one of three performance categories. In the qualitative arm of the study, stratified random sampling was used to select five CPOs from each performance strata to participate in an in-depth, semi-structured interview about their distribution activity. The interview guide and the data analysis were guided by Bowen's Feasibility Framework. The interviews were transcribed and analyzed using a content analysis approach by two research team members. All qualitative analyses were conducted in ATLAS.ti© V7. RESULTS: There was a total of 47 CPOs contacted and asked to be part of this study. Of them, 44 CPOs participated in the quantitative phase of the study. This phase revealed that all CPOs had existing relationships with organizations throughout the community such as pharmacies and schools that could act as points of distribution. Following the quantitative phase, 15 CPOs were selected for more in-depth interviews about their distribution practices. In the qualitative phase, this finding was reinforced through the theme "partnerships with local institutions and ability to implement the intervention at community events". Similarly, education promotion efforts were unanimously emphasized as a strategy to increase utilization of IHDP among end users. All CPOs indicated that the intervention was supplemental to their overall goals. CONCLUSION: CPOs have unparalleled access to community events, local institutions, and the general population they serve, thus, they have the potential to be active facilitators in implementing prevention interventions.

Physician perspective on the implementation of risk mitigation strategies when prescribing opioid medications: a qualitative analysis.

OBJECTIVE: To understand the physician perspective on the barriers and facilitators of implementing nine different opioid risk mitigation strategies (RMS) when prescribing opioid medications. METHODS: We created and dispersed a cross-sectional online survey through the Qualtrics© data collection platform among a nationwide sample of physicians licensed to practice medicine in the United States who have prescribed an opioid medication within the past year. The responses were analyzed using a deductive thematic analysis approach based on the Consolidated Framework for Implementation Research (CFIR) to ensure a holistic approach to identifying the barriers and facilitators for each RMS assessed. In concordance with this method, the themes and codes for the thematic analysis were defined prior to the analysis. The five domains within the CFIR were used as themes and the 39 nested constructs were treated as the codes. Two members of the research team independently coded the transcripts and discussed points of disagreement until consensus was reached. All analyses were conducted in ATLAS.ti© V7. RESULTS: The completion rate for this survey was 85.1% with 273 participant responses eligible for analysis. Intercoder reliability was calculated to be 82%. Deductive thematic analysis yielded 2,077 descriptions of factors affecting implementation of the nine RMS. The most salient code across all RMS was Knowledge and Beliefs about the Intervention, which refers to individuals' attitudes towards and value placed on the intervention. Patient Needs and Resources, a code referring to the extent to which patient needs are known and prioritized by the organization, also emerged as a salient code. The physicians agreed that the patient perspective on the issue is vital to the uptake of each of the RMS. CONCLUSIONS: This deductive thematic analysis identified key points for actionable intervention across the nine RMS assessed and established the importance of patient concordance with physicians when deciding on a course of treatment.

The impact of the mainstreaming addiction treatment act and associated legislative action on pharmacy practice.

The recent passage of the Mainstreaming Addiction Treatment (MAT) Act will expand access to treatment for opioid use disorder (OUD) by eliminating prescriber registration requirements introduced as part of the Drug Abuse Treatment Act (DATA) of 2000. Without the X-Waiver, and Drug Enforcement Administration (DEA) registered prescriber can now prescribe buprenorphine. Eliminating DATA-2000 registration is the first step in improving access to buprenorphine, but additional barriers, including unclear restrictions on wholesale buprenorphine supply and insurance coverage, remain. Recently, the DEA formally clarified that suspicious order monitoring programs were managed entirely by wholesalers and manufacturers and that DEA does not set suspicious order monitoring limits. In this commentary, we address the somewhat conflicting implications of the MAT Act and recent DEA guidance on buprenorphine dispensing in community pharmacies. We also discuss innovative practice models that leverage pharmacists' cognitive skills to manage pharmacotherapy for persons with OUD. Recent policy changes and emerging evidence suggest that pharmacists are better positioned than ever to provide low-barrier access to treatment for OUD and to show their value in this practice area by actively engaging patients with prescribed buprenorphine.

Delays to Reward Delivery Enhance the Preference for an Initially Less Desirable Option: Role for the Basolateral Amygdala and Retrosplenial Cortex.

Temporal costs influence reward-based decisions. This is commonly studied in temporal discounting tasks that involve choosing between cues signaling an imminent reward option or a delayed reward option. However, it is unclear whether the temporal delay before a reward can alter the value of that option. To address this, we identified the relative preference between different flavored rewards during a free-feeding test using male and female rats. Animals underwent training where either the initial preferred or the initial less preferred reward was delivered noncontingently. By manipulating the intertrial interval during training sessions, we could determine whether temporal delays impact reward preference in a subsequent free-feeding test. Rats maintained their initial preference if the same delays were used across all training sessions. When the initial less preferred option was delivered after short delays (high reward rate) and the initial preferred option was delivered after long delays (low reward rate), rats expectedly increased their preference for the initial less desirable option. However, rats also increased their preference for the initial less desirable option under the opposite training contingencies: delivering the initial less preferred reward after long delays and the initial preferred reward after short delays. These data suggest that sunk temporal costs enhance the preference for a less desirable reward option. Pharmacological and lesion experiments were performed to identify the neural systems responsible for this behavioral phenomenon. Our findings demonstrate the basolateral amygdala and retrosplenial cortex are required for temporal delays to enhance the preference for an initially less desirable reward.SIGNIFICANCE STATEMENT The goal of this study was to determine how temporal delays influence reward preference. We demonstrate that delivering an initially less desirable reward after long delays subsequently increases the consumption and preference for that reward. Furthermore, we identified the basolateral amygdala and the retrosplenial cortex as essential nuclei for mediating the change in reward preference elicited by sunk temporal costs.

Pattern of dopamine signaling during aversive events predicts active avoidance learning.

Learning to avoid aversive outcomes is an adaptive strategy to limit one's future exposure to stressful events. However, there is considerable variance in active avoidance learning across a population. The mesolimbic dopamine system contributes to behaviors elicited by aversive stimuli, although it is unclear if the heterogeneity in active avoidance learning is explained by differences in dopamine transmission. Furthermore, it is not known how dopamine signals evolve throughout active avoidance learning. To address these questions, we performed voltammetry recordings of dopamine release in the ventral medial striatum throughout training on inescapable footshock and signaled active avoidance tasks. This approach revealed differences in the pattern of dopamine signaling during the aversive cue and the safety period that corresponded to subsequent task performance. Dopamine transmission throughout the footshock bout did not predict performance but rather was modulated by the prior stress exposure. Additionally, we demonstrate that dopamine encodes a safety prediction error signal, which illustrates that ventral medial striatal dopamine release conveys a learning signal during both appetitive and aversive conditions.

Acute Stress Enhances Associative Learning via Dopamine Signaling in the Ventral Lateral Striatum.

Acute stress transiently increases vigilance, enhancing the detection of salient stimuli in one's environment. This increased perceptual sensitivity is thought to promote the association of rewarding outcomes with relevant cues. The mesolimbic dopamine system is critical for learning cue-reward associations. Dopamine levels in the ventral striatum are elevated following exposure to stress. Together, this suggests that the mesolimbic dopamine system could mediate the influence of acute stress on cue-reward learning. To address this possibility, we examined how a single stressful experience influenced learning in an appetitive pavlovian conditioning task. Male rats underwent an episode of restraint prior to the first conditioning session. This acute stress treatment augmented conditioned responding in subsequent sessions. Voltammetry recordings of mesolimbic dopamine levels demonstrated that acute stress selectively increased reward-evoked dopamine release in the ventral lateral striatum (VLS), but not in the ventral medial striatum. Antagonizing dopamine receptors in the VLS blocked the stress-induced enhancement of conditioned responding. Collectively, these findings illustrate that stress engages dopamine signaling in the VLS to facilitate appetitive learning.SIGNIFICANCE STATEMENT Acute stress influences learning about aversive and rewarding outcomes. Dopamine neurons are sensitive to stress and critical for reward learning. However, it is unclear whether stress regulates reward learning via dopamine signaling. Using fast-scan cyclic voltammetry as rats underwent pavlovian conditioning, we demonstrate that a single stressful experience increases reward-evoked dopamine release in the ventral lateral striatum. This enhanced dopamine signal accompanies a long-lasting increase in conditioned behavioral responding. These findings highlight that the ventral lateral striatum is a node for mediating the effect of stress on reward processing.

Bempedoic Acid: A New Drug for an Old Problem.

OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of bempedoic acid for low-density lipoprotein cholesterol (LDL-C) reduction. DATA SOURCES: A PubMed search was conducted from January 2000 to June 15, 2020, using the keyword bempedoic acid for phase III clinical trials published in the English language. STUDY SELECTION AND DATA EXTRACTION: Articles related to the Food and Drug Administration (FDA) approval of bempedoic acid and other trials relating to the safety and efficacy of this drug were included. DATA SYNTHESIS: The findings from this review show that bempedoic acid is a safe and effective option for lowering LDL-C levels in patients requiring LDL-C lowering for primary or secondary prevention of cardiovascular events. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Statin therapy remains the mainstay of treatment for both primary and secondary prevention. However, many patients cannot tolerate statin therapy because of statin-associated muscle symptoms. Bempedoic acid may be a reasonable adjunct for LDL-C reduction, though further evaluation of cardiovascular outcomes with bempedoic acid in this population is needed. CONCLUSIONS: The recent FDA approval of bempedoic acid offers an additional option for lowering LDL-C levels in patients with atherosclerotic cardiovascular disease or heterozygous familial hyperlipidemia. Additional data regarding effect on long-term cardiovascular outcomes with bempedoic acid are currently being studied.

Cocaine experience abolishes the motivation suppressing effect of CRF in the ventral midbrain.

Stress affects dopamine-dependent behaviors in part through the actions of corticotropin releasing factor (CRF) in the ventral tegmental area (VTA). For example, acute stress engages CRF signaling in the VTA to suppress the motivation to work for food rewards. In contrast, acute stress promotes drug-seeking behavior through the actions of CRF in the VTA. These diverging behavioral effects in food- and drug-based tasks could indicate that CRF modulates goal-directed actions in a reinforcer-specific manner. Alternatively, prior drug experience could functionally alter how CRF in the VTA regulates dopamine-dependent behavior. To address these possibilities, we examined how intra-VTA injections of CRF influenced cocaine intake and whether prior drug experience alters how CRF modulates the motivation for food rewards. Our results demonstrate that intra-VTA injections of CRF had no effect on drug intake when self-administering cocaine under a progressive ratio reinforcement schedule. We also found that a prior history of either contingent or noncontingent cocaine infusions abolished the capacity for CRF to reduce the motivation for food rewards. Furthermore, voltammetry recordings in the nucleus accumbens illustrate that CRF in the VTA had no effect on cocaine-evoked dopamine release. These results collectively illustrate that exposure to abused substances functionally alters how neuropeptides act within the VTA to influence motivated behavior.

Operant Costs Modulate Dopamine Release to Self-Administered Cocaine.

The costs associated with obtaining illicit drugs can fluctuate depending upon the relative drug availability. As a consequence of the changing costs, the effort that one must exert to obtain drugs is dynamic. Considerable evidence illustrates a critical role for dopamine in the ventral medial striatum in mediating drug reinforcement. However, little is known regarding how dopamine release is affected by changes in the costs associated with earning drugs. We used fast-scan cyclic voltammetry to determine how changes in the operant requirement affected dopamine release to self-administered cocaine in male rats. Dopamine release to cocaine infusions increased across trials during self-administration sessions using a fixed-ratio reinforcement schedule with a low operant requirement. However, increasing the operant requirement abolished the within-session elevation in dopamine release to drug rewards. This effect was not due to underlying changes in preinfusion dopamine levels and was not explained by cocaine levels in the brain. This within-session increase in dopamine release to cocaine infusions reemerged when the operant requirement was lowered. Under a progressive ratio reinforcement schedule, there was no increase in dopamine release to drug rewards across trials, which contrasts with prior studies demonstrating an increase in dopamine release to food rewards. Collectively, these findings illustrate that the influence of operant costs on reward-evoked dopamine release depends upon type of reward that can be earned (e.g., food or drug).SIGNIFICANCE STATEMENT The mesolimbic dopamine system is involved with mediating drug reinforcement. Although the costs associated with earning drugs are dynamic, no studies to date have examined how dopamine release to drug rewards is affected by changing costs. By performing fast-scan cyclic voltammetry recordings in rats self-administering cocaine, the present work demonstrates that changing the operant costs reversibly modulates the dopamine response to cocaine rewards. Furthermore, these findings highlight that the influence of costs on dopamine release to drug rewards differs from the established effect of costs on dopamine release to food rewards.

A comparison of anticoagulation, antiplatelet, and placebo treatment for patients with heart failure reduced ejection fraction in sinus rhythm: a systematic review and meta-analysis.

Previous meta-analyses have not recommended routine warfarin use in heart failure (HF) patients but included limited data on contemporary anticoagulants and practices. We conducted an updated meta-analysis in light of newer literature evaluating rivaroxaban in this patient population. The aim of this meta-analysis was to assess if anticoagulation is associated with a decrease in all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for HF exacerbation without an increased risk of major bleeding. A systematic search was conducted for randomized controlled trials to evaluate the use of antithrombotic therapy in patients with HF in sinus rhythm. Outcomes evaluated included all-cause mortality (ACM), non-fatal stroke, MI, hospitalization for HF exacerbation, and major bleeding. Five trials met criteria with a total of 9390 patients included. Four of the five trials evaluated warfarin use and one trial evaluated rivaroxaban. When anticoagulation was compared to control (antiplatelet and placebo groups), a significant reduction in ischemic stroke was found (OR 0.57; 95% CI, 0.42 to 0.78; P = 0.0005, I2 = 6.9%) and no significant difference was found in the risk of ACM, MI, or HF hospitalization. A significant increase in major bleeding was observed in the anticoagulation group when compared to the control group (OR 2.00; 95% CI, 1.45 to 2.75; P = < 0.0001, I2 = 25.79%). Anticoagulation in HF patients in normal sinus rhythm does not appear to reduce mortality rate, prevent MI, or decrease HF hospitalizations. Use reduces risk of ischemic stroke but is counterbalanced with an increase in major bleeding.

Is There Still a Role for Aspirin in Primary Prevention in Women in 2020?

PURPOSE OF REVIEW: Aspirin's place in primary prevention for females has not been well delineated and has been under increased scrutiny in light of recent literature and guideline recommendations. The purpose of this review is to discuss current literature reviewing aspirin use for primary prevention in women and to discuss when use is appropriate. RECENT FINDINGS: The Women's Health Study found no differences in major adverse cardiovascular events (MACE) in women randomized to aspirin vs. placebo, though a significant reduction was observed in women ≥ 65 years. More recent literature evaluated outcomes for primary prevention use in patients at increased cardiovascular risk, patients with diabetes, and patients who are elderly. These trials found either no benefit in MACE outcomes or a slight benefit accompanied by an increased risk of bleeding. Furthermore, no difference in outcomes were found in subgroup analyses comparing females receiving aspirin vs. placebo or comparing events in males vs. females. With improvements in risk factor reduction, such as blood pressure control, statin use, diabetes management, and smoking cessation, the role of aspirin for primary prevention in women is still uncertain. Aspirin use for primary prevention in females has failed to show a clear benefit except in women ≥ 65 years old, with a potential increase in bleeding events. An effort to better study aspirin in female patients would allow for better identification of women who would or would not benefit from therapy.

Prescription drug disposal: Products available for home use.

OBJECTIVE: Unused medications in the home are often improperly stored and may lead to unintentional harm, misuse, and diversion. Single-use disposal systems products allow consumers to safely inactivate unused medication and provide an environmentally friendly alternative to flushing medication down the toilet or discarding in the trash. The objective of this commentary was to review current medication disposal options and inform pharmacists of new products that may be used by patients to dispose of medications in the home setting. DATA SOURCES: Current recommendations on medication disposal from U.S. regulatory agencies (e.g., the Environmental Protection Agency) were reviewed and summarized comparatively. Information on the mechanism of action, price, and method of use of 8 new single-use disposal systems suitable for outpatient use were taken from each product manufacturer's website. SUMMARY: Eight single-use disposal systems were identified. Seven products used chemical deactivation to render medication safe for disposal, and 1 product allowed consumers to mail medication to a central processing facility for incineration. Products ranged in size from 2 oz to 1 gal, offering consumers the ability to dispose of anywhere from 60 to 3000 tablets per unit, respectively. Unit costs varied widely from $5 per single-use pouch to $190 for a 40-gal box intended for incineration. CONCLUSION: Pharmacists and consumers must consider cost, effectiveness, and environmental impact when recommending and selecting products for medication disposal at home. More research is needed to understand the cost-effectiveness of each disposal system and to identify strategies to encourage uptake by health systems and use by consumers. Including content on home medication disposal in pharmacist-continuing education activities and raising workforce awareness of these products are critical to improving public safety.

Management of Anticoagulation with Impella® Percutaneous Ventricular Assist Devices and Review of New Literature.

Cardiogenic shock is a life-threatening condition that may occur secondary to a variety of cardiac conditions, and may require temporary support with percutaneous ventricular devices like the Impella®. Anticoagulation in patients with Impella® devices can often be complicated due to unpredictable purge flow rates, pre-existing coagulopathy, or heparin allergies. The purpose of this article is to discuss the various options for anticoagulation in the setting of Impella®. The article will also describe recent updates (2014-current) in literature surrounding anticoagulation therapy for Impella® devices. At total of 228 articles were initially obtained through the PubMed search, with inclusion of 6 articles. A total of 51 patients had data in the six studies that were included in the review. Heparin for anticoagulation in the purge solution, at two different dextrose concentrations (5% and 20%), was associated with similar therapeutic activated partial thromboplastin time rates, thrombotic and bleeding events. One case series described the use of argatroban in the purge solution for anticoagulation in two patients with suspected heparin-induced thrombocytopenia, without bleeding or thrombotic complications. Pump thrombosis was not reported in any of the six studies. Anticoagulation in the setting of mechanical circulatory support devices is a challenging aspect of critical care. Institutions should have set protocols that clearly define the options for anticoagulation. Future studies that look at longer durations of support and possible operation of the Impella® device with a heparin-free purge solution are needed.

Health care practitioner counseling encourages disposal of unused opioid medications.

OBJECTIVE: The objective of this study was to estimate the association between health care practitioner counseling on medication disposal and disposal of unused opioid medications. DESIGN: A 41-item survey instrument was created and administered to a nationally representative panel of adult opioid users with chronic pain using a cross-sectional, internet survey design via Qualtrics®. PARTICIPANTS: Four hundred adult opioid users with chronic pain were randomly selected from the Qualtrics® panel-base to participate. SETTING: United States. OUTCOME MEASURES: The dependent variable, disposal of unused opioid medications, was assessed with a single item asking participants how often they had disposed of unused opioid medications in the past year. Multiple logistic regression was used to assess the association between opioid disposal and the receipt of health care practitioner counseling on medication disposal. RESULTS: A total of 400 surveys were completed. Participants were mostly white (70.8%) and under the age of 40 (54.1%). Less than one-half of all participants (44.5%) had disposed of opioid medications in the past year, while 60.75% had received health care practitioner counseling on disposal. Of those counseled, only 21.4% were counseled by a pharmacist. Flushing medication down the toilet (33%) was the most common method of opioid disposal. After adjustment for covariates, those who received health care practitioner counseling were more likely to have disposed of opioid medications in the past year (adjusted odds ratio 1.66, 95% CI 1.03-2.69). CONCLUSIONS: Participants who received counseling on opioid disposal were more likely to have disposed of unused opioid medications. Pharmacists are uniquely positioned to counsel patients on opioid disposal and thus must be active in preventing harm and diversion due to improperly stored opioid medications. This study demonstrates the need for enhanced provider education and policy to ensure that patients are adequately counseled on proper opioid disposal.

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive.

Stressors motivate an array of adaptive responses ranging from 'fight or flight' to an internal urgency signal facilitating long-term goals. However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments. Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal. An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry. Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors and other arousing environmental stimuli, acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF's capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.

Phasic Dopamine Transmission Reflects Initiation Vigor and Exerted Effort in an Action- and Region-Specific Manner.

Initiating a reward-seeking behavior involves deciding on an action, how fast to initiate the action (initiation vigor), as well as how much effort to exert. These processes are thought to involve the mesolimbic dopamine system. Dopamine levels in the ventral striatum rise before initiating a reliably reinforced behavior. However, it is unknown whether dopamine is similarly involved with unreinforced actions (inactive lever presses, premature food port entries, insufficient number of active lever presses). Furthermore, does the dopamine response when initiating an action reflect specific aspects of motivated behavior, such as initiation vigor and exerted effort? Here, we analyzed voltammetry recordings of dopamine levels in the nucleus accumbens (NAcc) core and shell in rats working for food under a progressive ratio reinforcement schedule. We examined dopamine levels when rats initiated distinct actions (active lever presses, inactive lever presses, food port entries) that were temporally separated from cue- and reward-evoked dopamine release. Active lever pressing bouts were preceded by elevated dopamine release in the NAcc shell, as well as in the NAcc core, although only when rats exhibited high initiation vigor. Dopamine levels were transiently reduced in the NAcc core following an unreinforced food port entry and were unchanged throughout the NAcc when initiating inactive lever presses. The effort exerted and vigor to initiate a bout of active lever presses were signaled by dopamine transmission in the NAcc core, but not in the NAcc shell. These results demonstrate that the dopamine response when initiating a behavior is both region- and action-specific. SIGNIFICANCE STATEMENT: Exogenous activation of the mesolimbic dopamine system facilitates motivated behavior. However, a direct relationship has not been established between endogenous phasic dopamine transmission and measures of motivation, such as the vigor to initiate an action and the effort exerted in a bout of activity. The present work demonstrates that the dopamine response when initiating an action depends both upon where dopamine is released and what action is performed. Furthermore, dopamine reflects measures of motivated behavior selectively within the nucleus accumbens core.

Phasic dopamine release in the nucleus accumbens in response to pro-social 50 kHz ultrasonic vocalizations in rats.

Rats emit ultrasonic vocalizations (USVs) that are thought to serve as situation-dependent affective signals and accomplish important communicative functions. In appetitive situations, rats produce 50 kHz USVs, whereas 22 kHz USVs occur in aversive situations. Reception of 50 kHz USVs induces social approach behavior, while 22 kHz USVs lead to freezing behavior. These opposite behavioral responses are paralleled by distinct brain activation patterns, with 50 kHz USVs, but not 22 kHz USVs, activating neurons in the nucleus accumbens (NAcc). The NAcc mediates appetitive behavior and is critically modulated by dopaminergic afferents that are known to encode the value of reward. Therefore, we hypothesized that 50 kHz USVs, but not 22 kHz USVs, elicit NAcc dopamine release. While recording dopamine signaling with fast-scan cyclic voltammetry, freely moving rats were exposed to playback of four acoustic stimuli via an ultrasonic speaker in random order: (1) 50 kHz USVs, (2) 22 kHz USVs, (3) time- and amplitude-matched white noise, and (4) background noise. Only presentation of 50 kHz USVs induced phasic dopamine release and elicited approach behavior toward the speaker. Both of these effects, neurochemical and behavioral, were most pronounced during initial playback, but then declined rapidly with subsequent presentations, indicating a close temporal relationship between the two measures. Moreover, the magnitudes of these effects during initial playback were significantly correlated. Collectively, our findings show that NAcc dopamine release encodes pro-social 50 kHz USVs, but not alarming 22 kHz USVs. Thus, our results support the hypothesis that these call types are processed in distinct neuroanatomical regions and establish a functional link between pro-social communicative signals and reward-related neurotransmission.

Balanced NMDA receptor activity in dopamine D1 receptor (D1R)- and D2R-expressing medium spiny neurons is required for amphetamine sensitization.

Signaling through N-methyl-D-aspartate-type glutamate receptors (NMDARs) is essential for the development of behavioral sensitization to psychostimulants such as amphetamine (AMPH). However, the cell type and brain region in which NMDAR signaling is required for AMPH sensitization remain unresolved. Here we use selective inactivation of Grin1, the gene encoding the essential NR1 subunit of NMDARs, in dopamine neurons or their medium spiny neuron (MSN) targets, to address this issue. We show that NMDAR signaling in dopamine neurons is not required for behavioral sensitization to AMPH. Conversely, removing NMDARs from MSNs that express the dopamine D1 receptor (D1R) significantly attenuated AMPH sensitization, and conditional, virus-mediated restoration of NR1 in D1R neurons in the nucleus accumbens (NAc) of these animals rescued sensitization. Interestingly, sensitization could also be restored by virus-mediated inactivation of NR1 in all remaining neurons in the NAc of animals lacking NMDARs on D1R neurons, or by removing NMDARs from all MSNs. Taken together, these data indicate that unbalanced loss of NMDAR signaling in D1R MSNs alone prevents AMPH sensitization, whereas a balanced loss of NMDARs from both D1R and dopamine D2 receptor-expressing (D2R) MSNs is permissive for sensitization.

The importance of coaching pharmacy students beyond their emotional intelligence assessment scores.

The teaching of emotional intelligence (EI) in pharmacy curriculums is an important part of a pharmacy learners' professional development and is crucial to improving interactions with health care providers and patients. However, the coaching of students to understand strengths and weaknesses related to their EI scores and how to facilitate these opportunities for personal growth is often the missing link from the teaching process. This commentary explores a college of pharmacy's experience with the incorporation of EI into the curriculum, with a focus on coaching students beyond the assessment numbers they receive. This requires placing emphasis on the broad applicability of EI, its personalization, and the actionable potential for growth. Guided reflections and individualized coaching, which differ from general teaching practices in pharmacy curricula today, can be used to promote the application of results as drivers for personal and professional success. Colleges/schools of pharmacy should consider investing resources in not only teaching students about EI but also coaching students as part of their professional journey.