Neurobiology of Obesity and Food Addiction: Looking at Disruptions in

the Mesolimbic Dopamine Pathway

Introduction Results
Obesity and food addiction have serious biological causes that often are Talia Menezes
overlooked in conversations about these diseases. Obesity and food addiction are Santa Clara University
highly associated with hyporesponsiveness of dopamine in the reward pathways.
For example, individuals often have lower levels of dopamine released in the
mesolimbic dopamine pathway in comparison to healthy individuals. This
contributes to patterns of hedonic feeding; eating foods based on their palatability Methods
despite being satiated. Hedonic feeding is reinforced by dopamine in the
mesolimbic pathway. Figure 2. Types of Mice Used. Mice were all adult
Through mice, the experiment demonstrates one possible neurobiological cause females and were between 10 to 12 weeks old at the
behind obesity and food addiction by examining a disruption of the mesolimbic beginning of the week2. The two types of mice used in
pathway. It explores the effect of depleting brain-derived neurotrophic factor this experiment were BDNF-depleted mutant mice
(BDNF) on evoked dopamine release from the Ventral Tegmental Area (VTA) and where BDNF was terminated everywhere in the brain
into the Nucleus Accumbens (NAc), in the mesolimbic dopamine pathway. except in the cerebellum, and wild type mice which
were used as the control2.

Background
Homeostatic feeding vs. Hedonic feeding Fig 6. Lower Amounts of Dopamine during
Homeostatic feeding refers to food consumption driven by the amount Evoked-Responses in BDNF Mutant Mice.
needed for sustainable energy. Top: Simplified visual of synaptic cleft. White
Hedonic eating is characterized by consumption of food because of its inward arrow represents equal amounts of
palatability rather than for nutritional purposes, despite how satiated the reuptake occurring. Bottom: Bar graph2 of
individual is4. molecules of dopamine determined by spike
Hedonic and homeostatic feeding mechanisms are not mutually amplitude and width. The third set uses
exclusive. However, an imbalance between the hedonic value and the nomifensine, a dopamine reuptake inhibitor.
homeostatic value of food is typical of eating disorders3. Lower amounts of dopamine seen with
Figure 3. Coronal view of the MDP in a mouse control of artificial cerebrospinal fluid
Mesolimbic Dopamine Pathway (MDP)
brain . Approximate locations of the NAc and (ACSF)(P<0.01) and with nomifensine.
Part of the food reward system which is activated in individuals struggling
VTA shown above. Mutant mice had a 43% decrease in
with obesity and food addiction6. Here, dopamine is involved in the
dopamine release in the NAc shell in
reinforcement of palatable foods rather than the pleasure aspect of food3. Figure 4. Anatomy of NAc. comparison to wild type mice (P<0.01)2.
Individuals with food addiction and obesity typically have Amperometric recordings were taken
hyporesponsiveness of DA in the reward system. It takes more food for from dopamine terminals in the NAc,
affected individuals to reach the same level of DA in a healthy individual6. both in the shell and the core. The
Food addiction is thus driven by overeating to compensate for the
hyporesponsiveness of DA (less DA released) in individuals with obesity and
dopamine neurons originated from Conclusions
the VTA1.
food addiction.
BDNF = DA = hedonic food consumption to compensate
Less dopamine being released to the Nac shell. This is not due to a pre-
stimulation difference in the amount of dopamine available to release and
the deficit of dopamine release is not due to reuptake of dopamine but
rather by decreased release of dopamine from the presynaptic mechanisms.
BDNF depletion disrupts the mesolimbic dopamine pathway and
exacerbates the hyporesponsiveness of DA characteristic of food addiction
and obesity.

Fig 5. Experimental Assay. Brain slices with VTA and NAc were taken from wild type and mutant
mice. Evoked secretion of dopamine was measured in brain slices from wild type and mutant mice. Future Explorations
5 Figure1. MDP in a human brain. Purple Electrodes were placed into the slices and then used to electrically stimulate the slices and record
arrow indicates transport of dopamine. dopamine levels in the slices3. Upper right-hand corner are amperometric traces3 of electrical Understanding that BDNF levels impact the mesolimbic pathway in a way that
stimulation-evoked dopamine release, showing the activity of the electrode. predicts food addiction and obesity is a first step in finding treatments for those
VTA & NAc: Anatomy of the MDP with the diseases caused by BDNF irregularities.
Dopamine is transported from the VTA and released into the NAc. A variety of
studies have found that DA neurons in the VTA increase DA levels in the NAc in Looking into other ways to behaviorally improve BDNF levels before turning to
an initial response to food reward. This is also seen in conditioned responses to medications would be a good next step. For example, BDNF levels can be
food6. References impacted by other factors such as high consumption of food2 and even
Thus, DA hypofunction in the mesolimbic pathway is associated with hedonic 1 Binder, Devin K., a nd Helen E. Scharfman. Brain-Derived Neurotrophic Factor. Growth factors (Chur, Switzerland) 22.3 (2004): 123131. exercise1. Increasing whole foods in persons diet or implementing physical
irregularities characterized by obesity and an increase in high-fat food PMC. Web. 27 Nov. 2017. activity in a daily routine could be treatments to try before pharmaceuticals.
consumpition6,7. 2 Cordeira, J. W., et a l. Brain-Derived Neurotrophic Factor Regulates Hedonic Feeding b y A cting o n the Mesolimbic Dopamine System.

Journal of Neuroscience, vol. 30, no. 7, 2010, pp. 25332541., doi:10.1523/jneurosci.5768-09.2010.

Brain-Derived Neurotrophic Factor (BDNF) 3 Egecioglu, Emil, et a l. Hedonic a nd i ncentive signals for b ody weight control. SpringerLink, Springer US, 22 Feb. 2011, On a larger scale, the experiment helps establish a neurobiological mechanism
BDNF is an important growth factor in the brain. It is essential to synaptic
doi.org/10.1007/s11154-011-9166-4.
4 Meye, Frank J., a nd Roger A .h. A dan. Feelings a bout food: the ventral tegmental a rea i n food reward a nd emotional eating. Trends i n
outside a persons control that can induce food addiction and obesity. It is not
plasticity, neural development and survival (Binder). Pharmacological Sciences, vol. 35, no. 1, 2014, pp. 3140., doi:10.1016/j.tips.2013.11.003. that persons fault nor can they get healthy without proper help and support.
BDNF is also important for satiety. Studies in rodents have shown that
5 Neuroscientifically Challenged. 2-Minute Neuroscience: Reward System. YouTube, YouTube, 13 Feb. 2015.
Food addiction and obesity often results from reasons beyond a persons
6 Volkow, N. D., et a l. Obesity a nd a ddiction: n eurobiological o verlaps. Obesity Reviews, vol. 14, n o. 1, 2012, p p. 218., d oi:10.1111/j.1467-
depleting BDNF induces excessive hunger, greatly increases food intake and 789x.2012.01031.x.
control. This understanding furthers the quality of support one receives from
results in obesity2. 7 Wu, Chun, et a l. Altered Dopamine Synaptic Markers i n Postmortem Brain o f Obese Subjects. Frontiers i n Human Neuroscience, vol. 11, professionals and helps one better cope with the diseases.
Mar. 2017, doi:10.3389/fnhum.2017.00386.
BDNF is expressed in dopamine-containing cells in the VTA and is delivered to
the NAc. BDNF is not critical for VTA dopamine neuron survival2 but later we
will see that the secretion of dopamine depends on BDNF .

December 3rd, 2017