Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous 
system (CNS) characterized by inflammation, but also degenerative changes. 
Besides neurological deficits, the rate of affective disorders such as 
depression and anxiety is at least six fold increased. Many aspects of MS can be 
mimicked in the animal model of myelin oligodendrocyte glycoprotein experimental 
autoimmune encephalomyelitis (MOG-EAE). Here we investigate behavioral changes 
in C57BL/6 mice suffering from mild MOG-EAE. In the later phase of the disease, 
mice were subjected to behavioral tests including the light-dark-box (LD Box), 
the acoustic startle response (SR) with a pre-pulse inhibition protocol as well 
as the learned helplessness (LH) paradigm. Behavioral data were correlated with 
the motor performance in an open field and rotarod test (RR). In the RR and open 
field, there was no significant difference in the motor performance between 
controls and mice suffering from mild MOG-EAE. Yet EAE mice displayed an 
increased anxiety-like behavior with a 23% reduction of the time spent in the 
bright compartment of the LD Box as well as an increased SR. In the LH paradigm, 
mice suffering from MOG-EAE were twice as much prone to depressive-like 
behavior. These changes correlate with an increase of hippocampal tissue tumor 
necrosis factor alpha levels and neuronal loss in the hippocampus. Modulation of 
monoaminergic transmission by chronic application of the antidepressant 
amitriptyline resulted in a decreased startle reaction and increased hippocampal 
norepinephrine levels. These data imply that chronic inflammation in the CNS may 
impact on emotional responses in rodent models of anxiety.