of food craving Carrie R. Ferrario, PhD Oct 13, 2020 BBRF Meet the - - PowerPoint PPT Presentation

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of food craving Carrie R. Ferrario, PhD Oct 13, 2020 BBRF Meet the - - PowerPoint PPT Presentation

Jan 23, 2024 342 likes •788 views

Why did I eat that? Obesity and the neuroscience of food craving Carrie R. Ferrario, PhD Oct 13, 2020 BBRF Meet the Scientist Webinar Series Most often used food word Most often used activity word Peter Sheridan Dodds, University of

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Why did I eat that? Obesity and the neuroscience

  • f food craving

Carrie R. Ferrario, PhD

Oct 13, 2020

BBRF Meet the Scientist Webinar Series

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Peter Sheridan Dodds, University of Vermont

http://compstorylab.org/share/papers/alajajian2014a/maps.html

Most often used food word Most often used “activity” word

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Brain Systems Mediating Cue-Triggered Motivation

Adapted from Ferrario et al., J.NS, 2016

Rat brain

Adapted from Feder et al., 2008

Human brain

Glutamate = excites Dopamine = modulates

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Outline:

Cue-triggered motivation is stronger in obesity susceptible rats before obesity.

  • Food-seeking
  • Approach

Effects of sugary, fatty “junk-foods”

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Rodent models:

Selectively bred rat model

Body Weight Number of Subjects

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Is cue-triggered food-seeking enhanced in obesity-prone rats?

Selectively bred rat model

Body Weight Number of Subjects

(Levin et al., 1997)

Rodent models:

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Lever Press for Food (Food-Seeking)

Derman & Ferrario, Neuropharm., 2018 Active lever Inactive lever

10 20 30

Avg # Lever Presses

(Rs/min)

OP OR

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Learn Food/Cue Relationship

Derman & Ferrario, Neuropharm., 2018 Obesity-Prone Obesity-Resistant

Food cue Food cue Control cue Control cue

Food Cue Control Cue

Avg # Food Cup Entries

(Rs/min: CS-ITI)

Training Day

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No Food Given

Test: Does the food cue enhance food-seeking?

CS+ Tone CS- White Noise Food Cue Control Cue

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CS- (Control Cue)

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CS+ (Food Cue)

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CS+ CS- CS+ CS-

  • 2

2 4 6 8

Avg Active Lever Presses (Rs/min: CS-ITI)

Active Lever Responding

OP OR

*

Active Lever Presses (#/min) Derman & Ferrario, Neuropharm., 2018

Greater cue-triggered food-seeking in obesity-prone rats

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CS+ CS- CS+ CS-

  • 2

2 4 6 8

Avg Active Lever Presses (Rs/min: CS-ITI)

Active Lever Responding

OP OR

*

Active Lever Presses (#/min) Derman & Ferrario, Neuropharm., 2018

Greater cue-triggered food-seeking in obesity-prone rats

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1 2 3 4 5 6 7 8 10 20 30 40 50 60 Cue-triggered Approach

Session Avg # Food Cup Entries OP OR

Training Day Unpublished data

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Standard Rats:

no food given

Cue-triggered food-seeking Training

Junk-Food

Purina Lab Chow Junk-Food Mash Fat 4.5% 19.6% Protein 23% 14% Carbs 48.7% 58% Calories 4 kcal/g 4.5 kcal/g

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Weight (g) Week on JF

1 2 3 4 5 3 0 0 3 2 5 3 5 0 3 7 5 4 0 0 4 2 5 4 5 0 4 7 5

Gainer Non-Gainer

Standard Rats:

Junk-Food no food given

Cue-triggered food-seeking

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Weight after Junk-Food

Cue-triggered Food-Seeking

r = 0.56 P < 0.01

JF-Gainers JF-Non-Gainers Active Lever Presses (#/min) Cue-triggered Approach

Avg # Responses Derman and Ferrario, Beh Brain Res 2020 Robinson et al.,NPP 2015

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Take-homes 1:

1) Vulnerability factor in humans 2) Provides a useful tool

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MSN image by Grazyna Gorney, Kolb lab

Green=DRD1-CRE+ cells, rat

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“A-typical” CP-AMPA Receptors “Typical” AMPA Receptors

Very few in adult brain (~10%) Selectively blocked by NASPM Allow Ca2+ into cell (stronger excitation)

Glutamate Synapse Do CP-AMPARs mediate cue-triggered food-seeking?

Majority of AMPARs Allow Na+ into cell (excitation)

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Food Cue Training Lever Press for Food

Training

Derman & Ferrario, Neuropharm., 2018

Intra NAc infusion of:

  • Control
  • NASPM (blocks CP-AMPARs)

CP-AMPAR Blockade During Test

No Food Given

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Control CP-AMPAR Block Obesity Prone

Active Lever Presses (#/min)

Derman & Ferrario, Neuropharm., 2018

Activity of CP-AMPARs is needed for cue-triggered food-seeking.

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Does eating junk-foods enhance AMPARs? Do effects differ in obesity-prone & obesity-resistant rats?

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Chow (3 weeks) JF-Deprivation

Junk-food increases CP-AMPAR function

3 months

Standard Rats:

Oginsky et al., NPP, 2016

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Chow (2 weeks) JF-Deprivation 10 days

Selectively bred obesity-prone and obesity-resistant rats

Chow

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Junk-food increases CP-AMAPRs in obesity-prone but not obesity-resistant rats

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Oginsky et al., NPP, 2016

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Take-homes 2:

1) Changes in bran function occur in response to eating junk-food 2) Obesity-prone more sensitive to these effects

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Why different behavioral sensitivity & neural changes?

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Inherent enhancements in Medium Spiny Neuron function

MSN image by Grazyna Gorney

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Oginsky et al., Psychopharm, 2016 Oginsky et al., J. Physiol, 2019 Alonso-Caraballo & Ferrario, Horm & Beh, 2019

Females

# of Action Potentials

100 200 300 400 5 10 15

OP OR

*** MSNs fire more easily M/D

Injected current (pA)

Obesity-Resistant Obesity-Prone MSNs fire more easily

Injected current (pA)

Males

# of Action Potentials

50 100 150 200

  • 5

5 10 15 20

OP OR

* * *

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Outbred SD Rats OP OR Female F1 OR Female F1 OP

# of Action Potentials

* * * * * * * * M/D OR OP

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Why different behavioral sensitivity & neural changes? Fire more easily, easier to induce changes in cell function.

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Does junk-food enhance cue-triggered motivation?

Junk-Food

Approach to cue alone?

Training Food-cue Control Lab Chow

30 days

Chow (14 days) JF-Deprivation

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  • 2

2 4 6 8

Mean Food Cup Entries (CS-ITI: Rs/min)

Chow Junk-Food Con Food Cue Food Cue Con

Avg # Food Cup Entries

(#/min)

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  • 2

2 4 6 8

Mean Food Cup Entries (CS-ITI: Rs/min)

Chow Junk-Food Con Food Cue Food Cue Con Outstanding Questions: Effects greater in OP vs OR? How long lasting? Mechanisms?

Junk-food enhances cue-triggered approach

Avg # Food Cup Entries

(#/min)

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Current Lab Members: Tracy Fetterly, PhD# Julie Finnell, PhD Megan Wickens, PhD Amanda France Jacob Ormes Allison Nieto Anish Saraswat Sophia Dunlap Rachel Springsdorf$ Ongoing Collaborations: Travis Brown (U WY) Monica Dus (UM) Terry Robinson (UM) Past Lab Members: Yanaira Alonso-Caraballo, PhD@ Rebecca Derman, PhD+ Peter Vollbrecht, PhD# Max Oginsky, PhD#,* Emma Bergman Cameron Nobile

Trainee Funding: +F31DK111194, @F99NS108549, *F32DK112627A, #T32DA007268,$T32DA007281 Research Funding: R01-DK106188; R01-DK115526; R01- DA044204; R21-DA045277; Brain & Behavior Foundation

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Take-homes:

1) Junk-food changes in brain function before

  • besity

2) Obesity-prone more sensitive to junk-food & cues 3) Vulnerability factor 4) Rodent models are useful tools

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Work for Food Cue-triggered Approach Food Intake

Cue-triggered motivation is greater in obesity-prone females & varies with the cycle in obesity-prone, but not obesity-resistant rats.

Avg # Food Cup Entries (Resp/min; CS-ITI)

MD= Metestrus/Diestrus PE= Proestrus/Estrus

Alonso-Caraballo & Ferrario, Hormones & Behavior, 2019; BioRxiv; 669804