Behavioral plasticity: Role of neuropeptides in shaping feeding responses.

Behavioral plasticity refers to changes occurring due to external influences on an organism, including adaptation, learning, memory and enduring influences from early life experience. There are 2 types of behavioral plasticity: "developmental", which refers to gene/environment interactions affecting a phenotype, and "activational" which refers to innate physiology and can involve structural physiological changes of the body. In this review, we focus on feeding behavior, and studies involving neuropeptides that influence behavioral plasticity - primarily opioids, orexin, neuropeptide Y, and oxytocin. In each section of the review, we include examples of behavioral plasticity as it relates to actions of these neuropeptides. It can be concluded from this review that eating behavior is influenced by a number of external factors, including time of day, type of food available, energy balance state, and stressors. The reviewed work underscores that environmental factors play a critical role in feeding behavior and energy balance, but changes in eating behavior also result from a multitude of non-environmental factors, such that there can be no single mechanism or variable that can explain ingestive behavior.

Chronic Intermittent Sucrose Consumption Facilitates the Ability to Discriminate Opioid Receptor Blockade with Naltrexone in Rats.

The opioid antagonist naltrexone (NTX) decreases intake of preferred diets in rats at very low doses relative to doses needed to decrease intake of "bland" laboratory chow. In the absence of an opioid agonist, NTX is not discriminable using operant techniques. In the current study, we found that rats given intermittent access to a 25% sucrose solution learned to discriminate between various naltrexone doses and saline. None of the rats given only water learned to discriminate between naltrexone and saline. When access to the sucrose solution was discontinued for 14 days, the rats lost the ability to discriminate between NTX and saline. We also studied the changes of c-Fos IR in selected brain regions in rats treated with saline versus NTX that were drinking water or 25% sucrose. An injection of NTX or saline resulted in a significant drug, diet, and interaction effect in various brain regions associated with feeding behavior, particularly the amygdala, accumbens, and hypothalamic sites. Thus, we found that ingestion of a sucrose solution results in the ability of rats to reliably discriminate naltrexone administration. In addition, sucrose and naltrexone altered c-Fos IR in an interactive fashion in brain regions known to be involved in ingestion behavior.

Promoting Scientific Exchange and Student Training Through Scientific Meetings; Insights from a Joint Virtual Undergraduate Neuroscience Conference During the COVID-19 Pandemic.

Participation in scientific conferences is a fundamental part of neuroscience and student training. Many conference opportunities have been cancelled, limited, or changed in response to the COVID-19 pandemic. This paper is a conference report from a joint virtual 2021 meeting of two regional undergraduate neuroscience conferences, the Midwest/Great Lakes Undergraduate Research Symposium in Neuroscience (mGluRs) and the Midwest Regional Neuroscience Conference (MidBrains). We discuss our conference planning logistics, benefits and challenges of the virtual conference format, student feedback on the virtual meeting, additional benefits of a joint meeting, and "take home" messages and considerations for future conferences. We hope insights from our experience can benefit future conference organizers in planning scientific conferences, both for in-person and virtual settings.

The ASPET Mentoring Network: Enhancing Diversity and Inclusion through Career Coaching Groups within a Scientific Society.

Over the past decades, two persisting priorities in science, technology, engineering, and mathematics (STEM) training have been: 1) increasing the knowledge of and access to careers beyond academic scientist; and 2) increasing the diversity of the STEM workforce. Previous studies show that a uniquely constructed career coaching group provides strong support and progress for both priorities. This report extends this design into a more sustainable model that is positioned within the professional context of rising young scientists. This new model is based in the American Society for Pharmacology and Experimental Therapeutics (ASPET)-the ASPET Mentoring Network. Groups of PhD students and postdocs were assigned to an ASPET professional (academic or other career) member (the coach) with an initial meeting held the day before the society's annual meeting. The coaching groups interacted during the meeting and then virtually for a year. Extensive survey and interview evaluation data gathered from the first three cohorts (12 coaching groups) in 2016- 2018 provided strong evidence of the perceived and real benefits of the network. This new version of career coaching groups is both feasible and linked to career success due to its close association with a scientific society, peers, and coaches who share scientific identities and aspirations.

Effects of opioid receptor ligands in rats trained to discriminate 22 from 2 hours of food deprivation suggest a lack of opioid involvement in eating for hunger.

It is well accepted that opioids promote feeding for reward. Some studies suggest a potential involvement in hunger-driven intake, but they suffer from the scarcity of methodologies differentiating between factors that intersect eating for pleasure versus energy. Here, we used a unique food deprivation discrimination paradigm to test a hypothesis that, since opioids appear to control feeding reward, injection of opioid agonists would not produce effects akin to 22 h of food deprivation. We trained rats to discriminate between 22 h and 2 h food deprivation in a two-lever, operant discrimination procedure. We tested whether opioid agonists at orexigenic doses produce discriminative stimulus effects similar to 22 h deprivation. We injected DAMGO, DSLET, or orphanin FQ in the paraventricular hypothalamic nucleus (PVN), a site regulating hunger/satiety, and butorphanol subcutaneously (to produce maximum consumption). We assessed the ability of the opioid antagonist, naltrexone, to reduce the discriminative stimulus effects of 22 h deprivation and of the 22 h deprivation-like discriminative stimulus effects of PVN-injected hunger mediator, neuropeptide Y (NPY). In contrast to PVN NPY, centrally or peripherally injected opioid agonists failed to induce discriminative stimuli similar to those of 22 h deprivation. In line with that, naltrexone did not reduce the hunger discriminative stimuli induced by either 22 h deprivation or NPY administration in 2 h food-restricted subjects, even though doses used therein were sufficient to decrease deprivation-induced feeding in a non-operant setting in animals familiar with consequences of 2 h and 22 h deprivation. We conclude that opioids promote feeding for reward rather than in order to replenish lacking energy.

Effect of Oxytocin on Hunger Discrimination.

Centrally and peripherally administered oxytocin (OT) decreases food intake and activation of the endogenous OT systems, which is associated with termination of feeding. Evidence gathered thus far points to OT as a facilitator of early satiation, a peptide that reduces the need for a meal that has already begun. It is not known, however, whether OT can diminish a feeling of hunger, thereby decreasing a perceived need to seek calories. Therefore, in the current project, we first confirmed that intraperitoneal (i.p.) OT at 0.3-1 mg/kg reduces food intake in deprived and non-deprived rats. We then used those OT doses in a unique hunger discrimination protocol. First, rats were trained to discriminate between 22- and 2-h food deprivation (hungry vs. sated state) in a two-lever operant procedure. After rats acquired the discrimination, they were food-restricted for 22 h and given i.p. OT before a generalization test session. OT did not decrease 22-h deprivation-appropriate responding to match that following 2-h food deprivation, thus, it did not reduce the perceived level of hunger. In order to better understand the mechanisms behind this ineffectiveness of OT, we used c-Fos immunohistochemistry to determine whether i.p. OT activates a different subset of feeding-related brain sites under 22- vs. 2-h deprivation. We found that in sated animals, OT induces c-Fos changes in a broader network of hypothalamic and brain stem sites compared to those affected in the hungry state. Finally, by employing qPCR analysis, we asked whether food deprivation vs. sated state have an impact on OT receptor expression in the brain stem, a CNS "entry" region for peripheral OT. Fasted animals had significantly lower OT receptor mRNA levels than their ad libitum-fed counterparts. We conclude that OT does not diminish a feeling of hunger before a start of a meal. Instead OT's anorexigenic properties are manifested once consumption has already begun which is-at least to some extent-driven by changes in brain responsiveness to OT treatment in the hungry vs. fed state. OT should be viewed as a mediator of early satiation rather than as a molecule that diminishes perceived hunger.

Depression in neurodegenerative diseases: Common mechanisms and current treatment options.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and a major cause of disability worldwide. This neurological condition is commonly associated with neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD), and has a significant impact on the increasing burden of these neuropathologies. Over the past decades, some of the pathophysiological and molecular mechanisms that contribute to these diseases have been elucidated and these findings indicate that, despite presenting distinct features, there are several similarities between the neurobiological alterations that lead to MDD and neurodegeneration in AD, PD, and HD. For instance, disturbances in monoaminergic transmission and the hypothalamic-pituitary-adrenal (HPA) axis, increased oxidative and neuroinflammatory events, and impaired trophic support are thought to contribute to neuronal atrophy and death in all these diseases. In addition, neuroimaging findings have helped elucidate the structural and functional changes implicated in the relationship between depression and neurodegeneration, thus establishing a neuroanatomical signature to explain, at least in part, the comorbidity between MDD and AD, PD, and HD. The present review summarizes these findings and the current evidence regarding the effectiveness of common antidepressant therapies for the treatment of MDD in patients with these neurodegenerative diseases. This population is particularly vulnerable to the drawdowns of conventional antidepressant therapy (namely inadequate response and high risk of side effects), and the development of emerging therapeutic approaches to treat MDD in patients with AD, PD, and HD is thus of paramount importance to improve the quality of life of these individuals.

Effects of sibutramine and rimonabant in rats trained to discriminate between 22- and 2-h food deprivation.

OBJECTIVE: The objective of the study was to evaluate whether sibutramine and rimonabant, drugs that decrease food intake in human and non-human animals, affect the discriminative stimulus effects associated with acute food deprivation ("hunger"). MATERIALS AND METHODS: Rats were trained to discriminate between 22- and 2-h food deprivation in a two-lever choice procedure. After rats acquired the discrimination, subjects were food-restricted for 22 h and administered with sibutramine (0.32-10 mg/kg, p.o.) or rimonabant (0.32-10 mg/kg, s.c.) before a generalization test session. RESULTS: Sibutramine (3.2 mg/kg) produced significant decreases in 22-h deprivation-appropriate responding, response rates (resulting in lever pressing rates similar to those following 2-h food deprivation), and food intake measured 1 h after the generalization test. A larger sibutramine dose eliminated responding and significantly reduced food intake. Rimonabant did not alter the discriminative stimulus effects of 22-h food deprivation, but rimonabant did significantly reduce both response rates and food intake. CONCLUSION: Sibutramine appears to decrease food intake by reducing hunger sensations associated with food deprivation. In contrast, rimonabant does not alter the discrimination of acute food deprivation. The use of food-deprivation discrimination techniques may be useful in identifying the role of specific neuroactive compounds in eating stimulated by a sense of hunger and may aid in medication development for more effective treatments for obesity and other eating-related conditions.

Intraparaventricular neuropeptide Y and ghrelin induce learned behaviors that report food deprivation in rats.

Rats were trained to discriminate between 2 and 22-h food deprivation in a choice paradigm. During tests, 20 min of food consumption eliminated internal stimuli associated with 22-h food deprivation. In other tests, rats food-restricted for 2 h were given neuropeptide Y or ghrelin by administration into the paraventricular nucleus of the hypothalamus. Both neurochemicals induced effects similar to those following 22-h food restriction (increased behavior appropriate for 22-h deprivation). These findings suggest that internal stimuli produced by 22-h food deprivation are altered by food consumption and mimicked by feeding-inducing neurochemicals administered into a brain area associated with feeding regulation. Thus, hunger discrimination is a useful model to examine neurochemical and dietary factors that alter internal states associated with eating.

Chronic sucrose ingestion enhances mu-opioid discriminative stimulus effects.

Sucrose affects a variety of opioid-related behaviors. We hypothesized that, if sucrose ingestion alters opioidergic circuitry, opioid-induced discriminative stimulus effects would be enhanced following sucrose intake. In the present study, rats were trained to discriminate nalbuphine (3.2 mg/kg, s.c.) from saline in an operant choice procedure. After acquiring the discrimination, subjects were injected with a single nalbuphine dose (0.1-3.2 mg/kg) and given 30-min access to 30% sucrose or water. Sucrose consumption did not alter nalbuphine's discriminative stimulus effects under these conditions. During subsequent tests, training was suspended, and rats received continuous access to sucrose (9 days) or water (8 days). Chronic sucrose consumption increased the potency of nalbuphine to produce its discriminative stimulus effects by 3-fold. These findings suggest chronic sucrose consumption results in changes in opioid-system function that modulates the effects of exogenously administered opioids.

Illicit use of prescribed stimulant medication among college students.

The authors investigated illicit use of stimulant medications at a midwestern university. They used a questionnaire to (a) examine the extent to which university students illicitly used stimulant medications prescribed for attention-deficit hyperactivity disorder; (b) determine why college students abused such drugs; and (c) identify the factors that predicted illicit use of prescribed stimulant medication. Findings revealed that 17% of 179 surveyed men and 11% of 202 women reported illicit use of prescribed stimulant medication. Forty-four percent of surveyed students stated that they knew students who used stimulant medication illicitly for both academic and recreational reasons. Students reported they experienced time pressures associated with college life and that stimulants were said to increase alertness and energy. Regression analysis revealed that the factor that predicted men's use was knowing where to get easily acquired stimulant medication, whereas the main predictor for women was whether another student had offered the prescribed stimulants.

Our journey with neuropeptide Y: effects on ingestive behaviors and energy expenditure.

Clark and colleagues first described the robust orexigenic effects of neuropeptide Y (NPY) in 1984. Our group as well as Stanley et al. confirmed these effects in the same year. During the next 20 years, we investigated the effects of NPY on diet preferences, opioid-related feeding, distributed neural feeding networks, energy metabolism, motivation and discriminative stimulus effects. These data together with data from other laboratories indicate that NPY increases feeding, even when rats work for food; that NPY decreases energy expenditure, particularly by altering thermogenesis; and that NPY's effects on energy metabolism are mediated by a widely distributed neural network involving other neuroregulators known to be involved in energy regulation.

A forgotten resource critical to the future of behavior analysis: undergraduate psychology majors.

The demand for board-certified applied behavior analysts is not being met, and there is a perception that fewer students are exposed to systematic courses in basic and applied behavior analysis than was true a generation ago. This article outlines how we have successfully implemented an undergraduate curriculum in behavior analysis within a traditional department of psychology. Certification credentials offered by the Behavior Analysis Certification Board facilitated the approval of this curriculum, and the cultural practice selection contingencies that supported the creation of our curriculum in behavior analysis may be similar at other comprehensive universities. Advice for developing an undergraduate program in behavior analysis within a psychology department is outlined. We also summarize strategies we have used to attract talented students to the courses and the significant impact these strategies have had on the number of our graduates who pursue graduate training in basic and applied behavior analysis. Attracting the best and brightest students to behavior analysis is critical to the future of the field.