Rewarding Social Interaction in Rats Increases CaMKII in the Nucleus Accumbens

Calcium/calmodulin-dependent protein kinase II (CaMKII) is known to be involved in the sensitized locomotor responses and drug-seeking behavior to psychostimulants. However, little is known about the contribution of CaMKII signaling in the nucleus accumbens (NAc) in natural rewards such as social interaction. The present experiments explored the implication of CaMKII signaling in drug versus natural reward. In the NAc of rats expressing cocaine or social interaction conditioned place preference (CPP), αCaMKII activation was induced in those expressing social interaction but not cocaine CPP. In order to investigate the role of NAc CaMKII in the expression of reward-related learning of drug versus non-drug stimuli, we inhibited CaMKII through an infusion of KN-93, a CaMKII inhibitor, directly into the NAc shell or core, before the CPP test in a concurrent paradigm in which social interaction was made available in the compartment alternative to the one associated with cocaine during conditioning. Whereas vehicle infusions led to equal preference to both stimuli, inhibition of CaMKII by a KN-93 infusion before the CPP test in the shell but not the core of the NAc shifted the rats’ preference toward the cocaine-associated compartment. Altogether, these results suggest that social interaction reward engages CaMKII in the NAc.

Mindfulness-Oriented Recovery Enhancement remediates anhedonia in chronic opioid use by enhancing neurophysiological responses during savoring of natural rewards

Background Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT. Methods Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up. Results Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring. Conclusions MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Differential Aspects of Natural and Morphine Reward-Related Behaviors in Conditioned Place Preference Paradigm

Natural rewards are essential for animal survival. On the other hand, drug-seeking behaviours can be maladaptive and endanger survival. The present study was conducted to enhance our understanding of how animals respond to food and morphine as natural and drug rewards, respectively, in a conditioned place preference (CPP) paradigm. We designed a protocol to induce food-CPP and compare it as a natural reward with morphine-CPP in rats. The protocol for reward induction in all groups (foods and morphine) consisted of three phases: pre-test, conditioning, and post-test. In morphine groups, we injected morphine as a reward (5 mg/kg, s.c.), and for inducing natural-reward, we used two different protocols, by one of the rats were deprived of food for 24h. In the other method, rats were restricted for food for 14 days. During the conditioning period, animals received daily chow, biscuit, or popcorn as a reward inducer. Results revealed that CPP did not induce in food-deprived rats. A combination of food restriction (as a facilitator) and a biscuit or popcorn induced reward using CPP. In contrast, food deprivation did not facilitate food-CPP in response to regular food. Interestingly the CPP score of the group which received biscuit during a 7-day conditioning period was more than that of the morphine group. In conclusion, food restriction could be a better protocol than food deprivation to facilitate food reward.

Mindfulness in Treatment Approaches for Addiction — Underlying Mechanisms and Future Directions

Purpose of Review While the treatment of addictive disorders proves to be challenging, new treatment approaches that evolved around the concepts of mindfulness and acceptance have been utilized and investigated in recent years. Our goal is to summarize the efficacy and possible underlying mechanisms of mindfulness-based interventions (MBI) in addictive disorders. Recent Findings Various meta-analyses have suggested that MBIs show clinical efficacy in the treatment of addictive disorders. Considering the factors that impact addictive disorders, MBIs have been indicated to augment responsiveness to natural rewards in contrast to addiction-related cues as well as to increase top-down cognitive control, decrease subjective and physiological stress perception, and enhance positive affect. Summary In summary, MBIs hold promise in treating addictive disorders while larger randomized controlled trials with longitudinal study designs are needed to confirm their utility. Newest clinical endeavors strive to enhance the clinical utility of MBIs by augmentation or personalization.

Consolidating the Circuit Model for Addiction

Addiction is a disease characterized by compulsive drug seeking and consumption observed in 20–30% of users. An addicted individual will favor drug reward over natural rewards, despite major negative consequences. Mechanistic research on rodents modeling core components of the disease has identified altered synaptic transmission as the functional substrate of pathological behavior. While the initial version of a circuit model for addiction focused on early drug adaptive behaviors observed in all individuals, it fell short of accounting for the stochastic nature of the transition to compulsion. The model builds on the initial pharmacological effect common to all addictive drugs—an increase in dopamine levels in the mesolimbic system. Here, we consolidate this early model by integrating circuits underlying compulsion and negative reinforcement. We discuss the genetic and epigenetic correlates of individual vulnerability. Many recent data converge on a gain-of-function explanation for circuit remodeling, revealing blueprints for novel addiction therapies. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Operant conditioning deficits and modified local field potential activities in parvalbumin-deficient mice

Altered functioning of GABAergic interneurons expressing parvalbumin (PV) in the basal ganglia-thalamo-cortical circuit are likely to be involved in several human psychiatric disorders characterized by deficits in attention and sensory gating with dysfunctional decision-making behavior. However, the contribution of these interneurons in the ability to acquire demanding learning tasks remains unclear. Here, we combine an operant conditioning task with local field potentials simultaneously recorded in several nuclei involved in reward circuits of wild-type (WT) and PV-deficient (PVKO) mice, which are characterized by changes in firing activity of PV-expressing interneurons. In comparison with WT mice, PVKO animals presented significant deficits in the acquisition of the selected learning task. Recordings from prefrontal cortex, nucleus accumbens (NAc) and hippocampus showed significant decreases of the spectral power in beta and gamma bands in PVKO compared with WT mice particularly during the performance of the operant conditioning task. From the first to the last session, at all frequency bands the spectral power in NAc tended to increase in WT and to decrease in PVKO. Results indicate that PV deficiency impairs signaling necessary for instrumental learning and the recognition of natural rewards.

Implementation of Leadership Style in Increasing Local Government Innovation

The purpose of this study is to determine the implementation of leadership styles in increasing local government innovation. This research method is based on the approach used in this study is a qualitative approach. This research was conducted in North Luwu Regency, South Sulawesi Province, to be precise at the Regent Office of North Luwu Regency. Data collection was carried out through observation and interviews. The results showed that the leader has carried out his function as a spokesman. The output of the aforementioned activities has brought the good name of the North Luwu Regency Government as a regency that has the ability to speak professionally, where organizing international and national scale events require optimal lobbying and negotiations. The implementation of the leader in giving natural rewards to employees turns out to be able to improve performance and motivation on the pretext that the work given is an award because not everyone is able to complete the job well, on the other hand, employees feel that tasks that can be completed properly are opportunities for further increase his potential and competence so that it will be easier to get strategic positions in the future. Leaders play a role in creating a positive mindset towards developing potential employees from various dimensions, namely the dimensions of HR development, the dimensions of skill development, and the dimensions of decision making.

Oxytocin Attenuates Expression, but Not Acquisition, of Sucrose Conditioned Place Preference in Rats

Maladaptation of reward processing for natural rewards, such as sucrose or sugar, may play a role in the development of diseases such as obesity and diabetes. Furthermore, uncovering mechanisms to disrupt or reverse maladaptation of reward-seeking behaviors for natural reinforcers can provide insight into treatment of such diseases, as well as disorders such as addiction. As such, studying the effects of potential pharmacotherapeutics on maladaptive sugar-seeking behavior offers valuable clinical significance. Sucrose conditioned place preference (CPP) paradigms can offer insight into aspects of reward processes as it provides a way to assess acquisition and expression of context-reward associations. The present study examined the effect of peripheral oxytocin injections on sucrose CPP in rats. Oxytocin, when administered prior to CPP test, attenuated expression of sucrose CPP. However, oxytocin, when administered during sucrose conditioning, did not affect subsequent place preference. These findings suggest oxytocin sufficiently attenuates expression of sucrose-associated place preference.