Progressive-ratio Responding for Palatable High-fat and High-sugar Food in Mice

Sharma, Sandeep; Hryhorczuk, Cécile; Fulton, Stephanie

doi:10.3791/3754-v

Cited by 8 publications

(11 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After a training period of about 7-10 days when three successive sessions of obtaining equal and more than 20 pellets during the FR1 session of 45 min, mice were then engaged in consecutive PR sessions of 45 min. For the PR session, the number of lever presses required for one food pellet delivery followed the order (calculated by the formula [5e (R*0.2) ]−5 where R is equal to the number of food rewards already earned plus 1): 1, 2, 4, 6, 9, 12, 15, 20, and so on [40]. The maximal number of active lever presses performed to reach the final ratio was defined as the breakpoint, a value reflecting animals' motivation to get the food reward.…”

Section: Stereotactic Surgery For Cannula Implantationmentioning

confidence: 99%

Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia

Barrett

Nunez

Zhang

2021

Neuropsychopharmacol.

View full text Add to dashboard Cite

The neuropeptide oxytocin (OT) regulates important brain functions including feeding through activating OT receptors in multiple brain areas. Both OT fibers and OT receptors have been reported in the paraventricular thalamus (PVT), an area that was revealed to be important for the control of emotion, motivation, and food intake. However, the function and modulation of PVT OT signaling remain unknown. Here, we used a progressive ratio (PR) schedule of reinforcement to examine the role of PVT OT signaling in regulating the motivation for food and patch-clamp electrophysiology to study the modulation of OT on PVT neurons in brain slices. We demonstrate that PVT OT administration increases active lever presses to earn food rewards in both male and female mice under PR trials and OT receptor antagonist atosiban inhibits OT-induced increase in motivated lever presses. However, intra-PVT OT infusion does not affect food intake in normal conditions but attenuates hypophagia induced by stress and anxiety. Using patch-clamp recordings, we find OT induces long-lasting excitatory effects on neurons in all PVT regions, especially the middle to posterior PVT. OT not only evokes tonic inward currents but also increases the frequency of spontaneous excitatory postsynaptic currents on PVT neurons. The excitatory effect of OT on PVT neurons is mimicked by the specific OT receptor agonist [Thr4, Gly7]oxytocin (TGOT) and blocked by OT receptor antagonist atosiban. Together, our study reveals a critical role of PVT OT signaling in promoting feeding motivation to attenuate stress-induced hypophagia through exciting PVT neurons.

show abstract

Section: Stereotactic Surgery For Cannula Implantationmentioning

confidence: 99%

Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia

Barrett

Nunez

Zhang

2021

Neuropsychopharmacol.

View full text Add to dashboard Cite

show abstract

“…S1, G and H). Using operant behavioral tests under both fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement ( 25 ), we found that mice with VTA DA ablation had significantly lower active lever presses during both FR and PR sessions and breakpoints for food reward during PR sessions under fed but not fasted conditions (fig. S1, I to L).…”

Section: Resultsmentioning

confidence: 99%

“…After a training period of about 7 to 10 days when three successive sessions of obtaining equal and more than 20 pellets during the FR1 session of 45 min, mice were then engaged in consecutive PR sessions of 45 min. For the PR session, the number of lever presses required for one food pellet delivery followed the order (calculated by the formula [5 e ( R *0.2) ] − 5 where R is equal to the number of food rewards already earned plus 1): 1, 2, 4, 6, 9, 12, 15, 20, and so on ( 25 ). The maximal number of active lever presses performed to reach the final ratio was defined as the breakpoint, a value reflecting animals’ motivation to get the food reward.…”

Section: Methodsmentioning

confidence: 99%

Zona incerta dopamine neurons encode motivational vigor in food seeking

Ye,

Nunez,

Zhang

2023

Sci. Adv.

View full text Add to dashboard Cite

Energy deprivation triggers food seeking to ensure homeostatic consumption, but the neural coding of motivational vigor in food seeking during physical hunger remains unknown. Here, we report that ablation of dopamine (DA) neurons in zona incerta (ZI) but not ventral tegmental area potently impaired food seeking after fasting. ZI DA neurons and their projections to paraventricular thalamus (PVT) were quickly activated for food approach but inhibited during food consumption. Chemogenetic manipulation of ZI DA neurons bidirectionally regulated feeding motivation to control meal frequency but not meal size for food intake. Activation of ZI DA neurons promoted, but silencing of these neurons blocked, contextual memory associate with food reward. In addition, selective activation of ZI DA projections to PVT promoted food seeking for food consumption and transited positive-valence signals. Together, these findings reveal that ZI DA neurons encode motivational vigor in food seeking for food consumption through their projections to PVT.

show abstract

“…Instrumental Training and Progressive Ratio were used to assess appetitive learning and motivation (Sharma et al, 2012). Mice were food restricted up to 5 days a week with ad lib food at least 2 days a week to maintain at 85% of their free-feeding weight.…”

Section: Methodsmentioning

confidence: 99%

A mouse model of oral contraceptive exposure: depression, motivation, and the stress response

Schuh

Ahmed

Kwak

et al. 2023

Preprint

View full text Add to dashboard Cite

Hormonal contraceptives (HCs) regulate hormonal levels and cycles, and thereby affect many physiological outcomes including stress responsivity and acne. Many individuals also experience overall benefits in regulation of mood, yet up to 10% of HC users experience depression, anxiety, and other adverse events. Despite 60 years of availability, it remains unclear how HCs modulate brain, behavior, and mood. Here, we created and validated a mouse model of HC exposure to answer mechanistic questions arising from studies of human HC use. Young adult female C57Bl/6N mice received either daily oral hormone treatments or a control (10% sucrose) treatment to mimic daily oral contraceptive exposure in humans. Hormone treatments were a combination of ethinyl estradiol (EE) and a progestin—either levonorgestrel (LVNG) or drospirenone (DRSP)—in 10% sucrose. Translationally-relevant doses of EE+LVNG-exposure caused a specific anhedonia-like effect, without indication of broad depression- or anxiety-like presentations. EE+LVNG, but not EE+DRSP, suppressed the acute stress response, an effect consistent with that observed in human HC users. Importantly, the limited changes in behavioral outcomes, together with suppression of regular estrous cycling and suppression of the corticosterone response to acute stress demonstrate the validity and tractability of this model with which to investigate questions difficult to study in human subjects. Thus, this model will be important for identifying mechanisms and risks for adverse effects of HCs on mood that will contribute to a more personalized approach to HC prescribing strategies.

show abstract

Progressive-ratio Responding for Palatable High-fat and High-sugar Food in Mice

Cited by 8 publications

References 6 publications

Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia

Oxytocin activation of paraventricular thalamic neurons promotes feeding motivation to attenuate stress-induced hypophagia

Zona incerta dopamine neurons encode motivational vigor in food seeking

A mouse model of oral contraceptive exposure: depression, motivation, and the stress response

Contact Info

Product

Resources

About