The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH) and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc) and ventral pallidum (VP), in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (“liking”) and motivational incentive salience (“wanting”) of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating vs. intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including “liking” and “wanting” for food rewards.

The nucleus accumbens (NAc) contains multiple subpopulations of medium spiny neurons (MSNs). One subpopulation expresses D1-type dopamine receptors, another expresses D2-type receptors, and a third expresses both. The relative roles in NAc of D1 neurons versus D2 neurons in appetitive motivation were assessed here. Specifically, we asked whether D1-Cre mice would instrumentally seek optogenetic self-stimulation specifically targeted at D1 MSNs in NAc, and similarly if D2-Cre mice would self-stimulate D2 neurons in NAc. Mice were implanted with Cre-targeted channelrhodopsin (ChR2) virus and optic fibers in NAc. Subsequently, mice could earn brief NAc laser illuminations by actively touching a metal spout in one task, or by going to a particular location in a separate task. Results indicated that D1 neuronal excitation in NAc supported intense self-stimulation in both tasks. D1-Cre mice earned hundreds to thousands of spout-touches per half-hour session, and also sought out locations that delivered NAc laser to excite D1 MSNs. By comparison, D2 ChR2 mice showed lower but still positive levels of self-stimulation in the spout-touch task, earning dozens to hundreds of NAc laser illuminations. However, in the location task, D2 mice failed to show positive self-stimulation. If anything, a few D2 individuals gradually avoided the laser location. Brain-wide measures indicated that D1 and D2 stimulations in NAc recruited heavily overlapping patterns of Fos activation in distant limbic structures. These results confirm that excitation of D1 MSNs in NAc supports strong incentive motivation to self-stimulate. They also suggest that excitation of D2 neurons in NAc supports self-stimulation under some conditions, but fails under others and possibly may even shift to negative avoidance.

Many Ohio Head Start children do not receive dental care. Medicaid and patient age were primary dental office limitations that are partly offset by the role Head Start plays in ensuring dental care. Dentists, Head Start staff, and parents/caregivers have different perspectives on the problem of access to dental care.

Social/peer influences are among the strongest predictors of adolescent drug use. However, this important subject does not get much attention in pre-clinical studies. We recently observed that exposure to different social partners modulates morphine locomotor sensitization. Sensitivity to the hyper-locomotor response of drugs of abuse is a predictor of sensitivity to other drug-induced behaviors. Thus, this study examined how exposure to different social partners affected the rewarding properties of morphine. All animals were group-housed four per cage in one of two conditions referred to as 'only' and 'cage-mates'. In the mixed treatment condition, morphine- and saline-treated mice were housed together. These groups are referred to as 'morphine cage-mates' and 'saline cage-mates', respectively. In the separated treatment conditions, all mice in the cage received morphine (i.e. 'morphine only') or saline (i.e. 'saline only'), and cages were visually separated from each other. All animals were subsequently individually tested for the acquisition of morphine conditioned place preference (CPP) following one conditioning session with 10, 20 or 40 mg/kg morphine or saline. As expected, one conditioning session established morphine CPP in the morphine only animals, but not in the saline only animals. Notably, morphine CPP was not acquired by the morphine cage-mate animals. Additionally, 40 mg/kg morphine was sufficient to establish morphine CPP in the saline cage-mate animals. These results indicate that social environment has an effect on the rewarding properties of morphine. It suggests that exposure to different peers can alter the abuse potential of opioids and potentially other illicit drugs.

Microinjections of a glutamate AMPA antagonist (DNQX) in medial shell of nucleus accumbens (NAc) can cause either intense appetitive motivation (i.e., 'desire') or intense defensive motivation (i.e., 'dread'), depending on site along a flexible rostrocaudal gradient and on environmental ambience. DNQX, by blocking excitatory AMPA glutamate inputs, is hypothesized to produce relative inhibitions of NAc neurons. However, given potential alternative explanations, it is not known whether neuronal inhibition is in fact necessary for NAc DNQX microinjections to generate motivations. Here we provide a direct test of whether local neuronal inhibition in NAc is necessary for DNQX microinjections to produce either desire or dread. We used optogenetic channelrhodopsin (ChR2) excitations at the same local sites in NAc as DNQX microinjections to oppose relative neuronal inhibitions induced by DNQX in female and male rats. We found that same-site ChR2 excitation effectively reversed the ability of NAc DNQX microinjections to generate appetitive motivation, and similarly reversed ability of DNQX microinjections to generate defensive motivation. Same-site NAc optogenetic excitations also attenuated recruitment of Fos expression in other limbic structures throughout the brain, which was otherwise elevated by NAc DNQX microinjections that generated motivation. However, to successfully reverse motivation generation, an optic fiber tip for ChR2 illumination needed to be located within Ͻ1 mm of the corresponding DNQX microinjector tip; that is, both truly at the same NAc site. Thus, we confirm that localized NAc neuronal inhibition is required for AMPA-blocking microinjections in medial shell to induce either positively-valenced 'desire' or negatively-valenced 'dread'.

Mitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrate that cocaine affects mitochondrial dynamics and morphological characteristics within the nucleus accumbens (NAc). Further, mitochondria are differentially regulated by cocaine in dopamine receptor-1 containing medium spiny neurons (D1-MSNs) vs dopamine receptor-2 (D2)-MSNs. However, there is little understanding into cocaine-induced transcriptional mechanisms and their role in regulating mitochondrial processes. Here, we demonstrate that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Moreover, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial nuclear genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Further, blunting Egr3 expression in D1-MSNs blocks cocaine-enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reduction of D1-MSN Egr3 expression attenuates cocaine-induced enhancement of small-sized mitochondria, causally demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts mitochondrial dynamics and morphology by Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts; indicating roles for these molecular mechanisms in neuronal function and plasticity occurring with cocaine exposure.

Brain-derived neurotrophic factor (BDNF) has a critical role in stress response including neuropsychiatric disorders that are precipitated by stress, such as major depressive disorder (MDD). BDNF acts through its full-length BDNF receptor tyrosine kinase B (TrkB) to trigger a pro-plasticity effect. In contrast, the truncated isoform of the BDNF receptor (TrkB.t1) triggers an anti-plasticity effect. In stress outcomes, BDNF acting in the hippocampus has a stress resilience effect, and, inversely, in the nucleus accumbens (NAc), BDNF acts as a stress susceptible molecule. It is unknown if BDNF-TrkB acts on a specific NAc projection neuron, i.e., medium spiny neuron (MSN or spiny projection neuron), a subtype in stress outcomes. To determine this, we performed chronic social or vicarious witness defeat stress (CSDS or CWDS) in mice expressing TrkB.t1 in dopamine receptor 1 or 2 containing MSNs (D1- or D2-MSNs). Our results showed that TrkB.t1 overexpression in NAc D2-MSNs prevented the CSDS-induced social avoidance or other stress susceptible behaviors in male and female mice. We further showed that this overexpression in D2-MSNs blocked stress susceptible behavior induced by intra-NAc BDNF infusion. In contrast, our results demonstrate that overexpression of TrkB.t1 on NAc D1-MSNs facilitates the SDS susceptible behaviors. Our study provides enhanced details into the NAc cell subtype role of BDNF-TrkB signaling in stress outcomes.

U.S. nutrition labeling regulations require the declaration of sodium content on food products. Accurate and reproducible determination of Na in foods with low Na content (<140 mg/serving) is challenging because of laboratory contamination. Within-laboratory performance of inductively coupled plasma/MS (ICP/MS), flame atomic absorption spectrophotometry (FAAS), ion-selective electrode (ISE), and potentiometric titration of chloride ion were evaluated in 17 low-sodium foods. For 13 types of food, statistically significant differences (P < 0.05) exist between the within-day and/or interday means obtained by ICP/MS, FAAS, and ISE. Median within-day and interday precent RSD values were 2.7 and 6.1, 3.5 and 3.2, and 5.6 and 6.2, respectively, by ICP/MS, FAAS, and ISE. The fewest matrix effects were found with ICP/MS, followed by FAAS, and ISE. FAAS gave higher results in a variety of matrixes when compared to ICP/MS and/or ISE. ISE did not perform well in fatty foods or at very low Na concentrations. Manufacturers' Nutrition Facts Panel sodium declarations exceeded levels found by analysis in >70 of the foods. Analysis of chloride content does not produce reliable Na estimates in low-sodium foods, even when added sodium chloride is present. Methodological issues and contamination sources are discussed.