scholarly journals The minimal behavioral time window for reward conditioning in the nucleus accumbens of mice

2019 ◽  
Author(s):  
Kenji Yamaguchi ◽  
Yoshitomo Maeda ◽  
Takeshi Sawada ◽  
Yusuke Iino ◽  
Mio Tajiri ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Animal Studies ◽  
Time Window ◽  
D1 Receptor ◽  
Temporal Precision ◽  
Minimal Time ◽  
Optogenetic Stimulation ◽  
The Us ◽  
Eligibility Trace ◽  
Reward Conditioning

AbstractThe temporal precision of reward-reinforcement learning is determined by the minimal time window of the reward action—theoretically known as the eligibility trace. In animal studies, however, such a minimal time window and its origin have not been well understood. Here, we used head-restrained mice to accurately control the timing of sucrose water as an unconditioned stimulus (US); we found that the reinforcement effect of the US occurred only within 1 s after a short tone of a conditioned stimulus (CS). The conditioning required the dopamine D1 receptor and CaMKII signaling in the nucleus accumbens (NAc). The time window was not reduced by replacing CS with optogenetic stimulation of the synaptic inputs to the NAc, which is in agreement with previous reports on the effective dopamine timing of NAc synapses. Thus, our data suggest that the minimal reward time window is 1 s, and is formed in the NAc.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

scholarly journals Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens.

2022 ◽  
Author(s):  
Bridget A Matikainen-Ankney ◽  
Alex A Legaria ◽  
Yvan M Vachez ◽  
Caitlin A Murphy ◽  
Yiyan A Pan ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Food Reward ◽  
Ex Vivo ◽  
D1 Receptor ◽  
Physical Work ◽  
Projection Neurons ◽  
Food Motivation ◽  
Obese Mice ◽  
Food Seeking

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with both in vivo electrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. With ex vivo slice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPN activity in obese mice. Finally, blocking synaptic transmission from D1SPNs decreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNs during food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNs in the development of diet-induced obesity, identifying a novel potential therapeutic target.

scholarly journals The Use and Misuse of Historical Controls in Regulatory Toxicology: Lessons from the CLARITY-BPA Study

Endocrinology ◽  
2019 ◽  
Vol 161 (5) ◽  
Author(s):  
Laura N Vandenberg ◽  
Gail S Prins ◽  
Heather B Patisaul ◽  
R Thomas Zoeller
Keyword(s):  
Drug Administration ◽  
Animal Studies ◽  
Ethinyl Estradiol ◽  
Food And Drug Administration ◽  
Endocrine Disrupting Chemicals ◽  
Pituitary Neoplasms ◽  
Control Data ◽  
Endocrine Disrupting ◽  
The Us ◽  
Historical Controls

Abstract For many endocrine-disrupting chemicals (EDCs) including Bisphenol A (BPA), animal studies show that environmentally relevant exposures cause harm; human studies are consistent with these findings. Yet, regulatory agencies charged with protecting public health continue to conclude that human exposures to these EDCs pose no risk. One reason for the disconnect between the scientific consensus on EDCs in the endocrinology community and the failure to act in the regulatory community is the dependence of the latter on so-called “guideline studies” to evaluate hazards, and the inability to incorporate independent scientific studies in risk assessment. The Consortium Linking Academic and Regulatory Insights on Toxicity (CLARITY) study was intended to bridge this gap, combining a “guideline” study with independent hypothesis-driven studies designed to be more appropriate to evaluate EDCs. Here we examined an aspect of “guideline” studies, the use of so-called “historical controls,” which are essentially control data borrowed from prior studies to aid in the interpretation of current findings. The US Food and Drug Administration authors used historical controls to question the plausibility of statistically significant BPA-related effects in the CLARITY study. We examined the use of historical controls on 5 outcomes in the CLARITY “guideline” study: mammary neoplasms, pituitary neoplasms, kidney nephropathy, prostate inflammation and adenomas, and body weight. Using US Food and Drug Administration–proposed historical control data, our evaluation revealed that endpoints used in “guideline” studies are not as reproducible as previously held. Combined with other data comparing the effects of ethinyl estradiol in 2 “guideline” studies including CLARITY-BPA, we conclude that near-exclusive reliance on “guideline” studies can result in scientifically invalid conclusions.

Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats

Neuroscience ◽  
2010 ◽  
Vol 171 (3) ◽  
pp. 779-787 ◽  
Author(s):  
J. Alsiö ◽  
P.K. Olszewski ◽  
A.H. Norbäck ◽  
Z.E.A. Gunnarsson ◽  
A.S. Levine ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Receptor Gene ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Palatable Food ◽  
Diet Induced Obesity ◽  
Obesity Phenotype ◽  
Receptor Gene Expression

Region-specific elevation of D1 receptor-mediated neurotransmission in the nucleus accumbens of SHR, a rat model of attention deficit/hyperactivity disorder

2012 ◽  
Vol 63 (4) ◽  
pp. 547-554 ◽  
Author(s):  
Yukihiro Ohno ◽  
Motoki Okano ◽  
Atsushi Masui ◽  
Junta Imaki ◽  
Mika Egawa ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Nucleus Accumbens ◽  
Rat Model ◽  
Attention Deficit ◽  
D1 Receptor ◽  
Hyperactivity Disorder

scholarly journals Effects of systemic or nucleus accumbens-directed dopamine D1 receptor antagonism on sucrose seeking in rats

2011 ◽  
Vol 216 (2) ◽  
pp. 219-233 ◽  
Author(s):  
Jeffrey W. Grimm ◽  
John H. Harkness ◽  
Christine Ratliff ◽  
Jesse Barnes ◽  
Kindsey North ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine D1 Receptor ◽  
D1 Receptor ◽  
Receptor Antagonism

Sexual experience alters D1 receptor-mediated cyclic AMP production in the nucleus accumbens of female Syrian hamsters

Synapse ◽  
2004 ◽  
Vol 53 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Katherine C. Bradley ◽  
Amanda J. Mullins ◽  
Robert L. Meisel ◽  
Val J. Watts
Keyword(s):  
Nucleus Accumbens ◽  
Cyclic Amp ◽  
Sexual Experience ◽  
D1 Receptor ◽  
Syrian Hamsters
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