ROLE OF BRAIN DERIVED NEUROTROPHIC FACTOR IN FOOD REWARDED BEHAVIOUR, IMPLICATIONS FOR THE STUDY OF OBESITY

C.M. Olarte-Sánchez, L. Valencia-Torres & L.K Heisler.

Rowett Institute of Nutrition and Health, The University of Aberdeen UK,.

INTRODUCTION OBJECTIVES METHODS

• Behavioural training
Food intake is a complex behaviour THE PROGRESSIVE RATIO SCHEDULE
controlled by the interaction between 1.To determine whether depletion of BDNF in the VTA
LEVER PRESS

homeostatic and reward-related processes. influences the effort to work to obtain high palatable RESPONSES COMPUTER .

food. FOOD-PELLET
• Brain-derived neurotrophic factor (BDNF) is REINFORCERS

a secreted protein expressed in numerous

brain regions that produces a profound effect 2.To determine whether different kinds of palatable
on food intake and body weight. Genetic food further affect the effort to work for food.
THE NUMBER OF RESPONSES NEEDED TO EARN A
inactivation of brain or ventromedial REINFORCER (N) IS PROGRESSIVELY INCREASED
hypothalamus (VMH) BDNF produces responses

produces hyperphagia and increased body 3.To asses whether the withdrawal of ad libitum reinforcers
* * * * *
weight on a standard chow (SC) diet [1] access to high fat food further increase the willingness
to work for highly palatable food (chocolate pellets As the ratio increases the number of responses decline
• The mesolimbic dopamine system, which is and sucrose). eventually the subject stops responding: the ‘break point’
related with the regulation of both motivated (BP). Although the BP can encapsulate motor
and reward seeking behaviour, is also related impairment it has traditionally been used as a measure of
the reinforcer efficacy.
with the consumption and motivation for 4.To evaluate changes in body weight as a consequence
drugs and palatable food [2,3]. of the change of reinforcers. Surgery
• Selective genetic inactivation of BDNF 16 male BDNF loxP mice, maintain on ad-libitum chow
intake. BDNF was removed in the VTA by infusing
within the ventral tegmental area (VTA)
adeno-associated viral (AAV) vectors encoding for Cre
produces hyperphagia and increased body recombinase or a mCherry.
weight on a high fat diet [4].
• Furthermore BDNF overexpression in the
Ilustration of the site
VTA reduces sucrose intake which was of the infection.
interpreted as a reduction of anhedonia [5].

RESULTS Evaluation of food intake during the Pr schedule Effect of HFD on food intake and BW
200
* Break Point Exp
Ctr
Total food
Total Food intake
100
* (Dark cycle)
 Break point%

150
* 80
3
When provided with a
Food Intake (g)

60
100 HFD intake(g) 2 choice of HFD or chow,
40

20
Exp
Ctr
both groups preferred
50
0
1 Exp palatable HFD.
Ctr

0 BDNF VTA knockdown mice 0

Chow consumed significantly more food

ts

e
os
lle

100 compared to the controls during the

cr
Pe

Su

80 PR schedule [t(14)=2.9, p=0.005].

Chow intake(g)

*
Overall, mice lacking BDNF within the VTA (Exp) had a 60 Further analysis showed that this was Chow Intake
(Dark cycle)

higher break point (BP) compared to control (Ctr) mice 40 due to a significant increase of chow 3

[F(1,14)=4.8, p<0.05], indicating that mice lacking BDNF [t(14)=2.57, p=0.01] but not lard.
Chow intake(g)

20
2
within the VTA exerted more effort to obtain palatable food. 0

Lard
100 0
200
Exp
*
80
Break Point BW changes
Ctr
Lard intake(g)

8 HFD Exp
 Break point%

150 60
Ctr
 Increment on BW

40
6
100 20 HFD
(Dark cycle)
6 3
4
0
Body weight increment
50
HFD intake(g)

2
2
4
0
BW  (g)

*** 1
0
e

ed
g

Access to chocolate
ca

ov

Fat withdrawal from the home 2

m

Exp
in

pellets significantly
re

0
rd

cage further increased the effort to

rd
La

increase BW in BDNF Ctr High fat diet increased body

La

work for highly palatable food in

VTA knockdown mice. 0 weight (BW) in both groups
mice lacking BDNF within the
VTA (Exp) [F(1,14)=5.1, [F(1,14)=41.8, Pellet Sucrose Lard in cage

p<0.05]. p<0.0001]. Reinforcers

Metabolic assessment under HFD and CHOW CONCLUSIONS

Energy expenditure Respirtatory exchange ratio The higher breakpoint in BDNF VTA knockdown mice suggests not only a higher sensitivity to hedonic feeding but
0.95 also a higher vulnerability to withdrawal processes as indicating by a even higher breakpoint after lard removal
30 Exp from the home cage. The results are in agreement with previous studies supporting the reward deficiency syndrome
Ctr
0.90 hypothesis. According to this hypothesis, BDNF deletion in the VTA may lead to a reward deficiency situation
where the organism compensates by overeating to boost a deficient dopaminergic system.
VCO2/VO2

25
Kcal/h/kg

0.85 The fact the BDNF VTA knockdown mice did not show an increase in intake of lard or HFD may indicate that the
20
deletion of BDNF in the VTA may be more closely related with a preference of sugar based food compared to fat
0.80 based food.

15 0.75
r rs rs rs r Acknowledgements
ou ou rs rs rs
H ou ou ou H ou ou ou Supported by Rowett institute of Nutrition and Health, University of Aberdeen and Wellcome Trust.
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