October 10 , 2012
The Role of Dopamine and Serotonin in Anorexia Nervosa:
 Fladung, A.K., Grön, G., Grammer, K., Herrnberger, B., Schilly, E., Grasteit, S., Wolf, R.C., Walter, H.,
von Wietersheim, J. (2010). A neural signature of anorexia nervosa in the ventral striatal reward
system. Am J Psychiatry, 167(2), 206-212.
Fladung et al. observed activity of the ventral striatum via functional magnetic resonance
imaging in women with acute anorexia nervosa. They observed that the anorexia nervosa
participants showed significantly higher activation in the ventral striatum when processing
visual stimuli that presented underweight individuals. These results are significant because
they agree with animal study findings in that the ventral striatum reward pathway, which
includes dopaminergic neurons, plays a role in anorexia nervosa.
Animal studies assessing mechanisms of self-starvation under conditions of stress and diet suggest a pivotal role for the mesolimbic
reward system in the maintenance of core symptoms in anorexia nervosa, which is corroborated by initial empirical evidence in
human studies. The authors examined activity in the ventral striatal system in response to disease-specific stimuli in women with
acute anorexia nervosa.
Participants were 14 women with acute anorexia nervosa and 14 matched healthy comparison women who underwent functional
magnetic resonance imaging (fMRI) during evaluation of visual stimuli depicting a female body with underweight, normal weight, and
overweight canonical whole-body features according to standardized body mass indices. Participants were required to process each
stimulus in a self-referring way. Ratings for each weight category were used as the control task.
Behaviorally, women with anorexia nervosa provided significantly higher positive ratings in response to underweight stimuli than in
response to normal-weight stimuli, while healthy comparison women showed greater preference for normal-weight stimuli relative to
underweight stimuli. Functionally, ventral striatal activity demonstrated a highly significant group-by-stimulus interaction for
underweight and normal-weight stimuli. In women with anorexia nervosa, activation was higher during processing of underweight
stimuli compared with normal-weight stimuli. The reverse pattern was observed in healthy comparison women.
These findings are consistent with predictions in animal studies of the pivotal role of the human reward system in anorexia nervosa
and thus support theories of starvation dependence in maintenance of the disorder.
 Galusca, B., Costes, N., Zitos, N.G., Peyron, R., Bossu, C., Lang, F., Le Bars, D., Estour, B. (2008).
Organic background of restrictive-type anorexia nervosa suggested by increased serotonin 1A
receptor binding in right frontotemporal cortex of both lean and recovered patients: [18F]MPPF
PET scan study. Biol Psychiatry, 64(11), 1009-1013. 18
The authors studied the binding of [ F]MPPF, an antagonist of serotonin, to various brain
structures within the brains of individuals suffering from anorexia nervosa. They found that
[ F]MPPF selectively bound to regions within the frontal cortex, including the superior
temporal gyrus, inferior frontal gyrus, and temperoparietal junction, in lean AN patients.
The results of these studies support the current hypothesis that serotonin plays a central
role in food intake regulation, which I will be investigating in my review.
BACKGROUND: Serotonin (5-HT) pathway abnormalities were demonstrated in anorexia nervosa (AN). Brain imaging studies on 5-HT
receptors support this evidence. 4-(2-methoxyphenyl)-1-[2-(N-2-pyridinyl)-p-fluorobenzamido]-ethylpiperazine ([(18)F]MPPF) is a
selective 5-HT(1A) receptor antagonist with an affinity close to that of endogenous 5-HT.
METHODS: In 24 subjects including 8 lean restrictive-type AN patients, 9 recovered from restrictive-type AN subjects and 7 age-
matched control subjects, we assessed in vivo brain [(18)F]MPPF binding by positron emission tomography and eating-related
psychopathological traits. Inter-groups differences in [(18)F]MPPF binding were evaluated by voxel-based analyses.
RESULTS: Restrictive AN patients presented increased [(18)F]MPPF binding in a selective area of the right cortex including part of the
superior temporal gyrus, inferior frontal gyrus, parietal operculum, and temporoparietal junction. Striking regional similarities of
increased [(18)F]MPPF binding were found in recovered from AN subjects. Most of the psychiatric scores were increased in restrictive
AN patients, and elevated perfectionism and interpersonal distrust scores were noticed in subjects recovered from AN.
CONCLUSIONS: The persistent increased 5-HT(1A) receptor binding in frontotemporal region of recovered AN concomitantly with
specific psychopathological traits support the hypothesis of an organic dysfunction of this area and corroborates with previous
literature reports of AN cases induced by temporal lesions.
 Liang, N.C., Bello, N.T., Moran, T.H. (2011) Experience with activity based anorexia enhances
conditioned taste aversion in rats. Physiol Behav, 102(1), 51-57.
This study examined whether previous experience with the activity-based anorexia (ABA)
model in rats enhances food aversion learning and slow its extinction. The results suggested
that ABA rats had enhanced food aversion when they expe