Researchers found that two neurotransmitters are simultaneously released by neurons to signal the emotion of disappointment.
    
The ratio of the two neurotransmitters is what determines whether you feel a bit discouraged or totally downhearted, they said.
    
This dual firing of neurotransmitters is a rare event in the brain. Scientists know of only two other situations in which the brain uses a simultaneous combination of excitatory and inhibitory neurotransmitters, and neither of those situations involves mood, 'LiveScience' reported.
    
In the new study, a team of scientists led by Dr Roberto Malinow, a professor of neurobiology at the University of California, San Diego School of Medicine, found that two well-known neurotransmitters - glutamate and GABA, which is short for gamma-aminobutyric acid - are released simultaneously by neurons in a small region of the brain called the lateral habenula to signal the emotion of disappointment.
    
"The more glutamate is released relative to GABA, the greater the 'disappointment' signal in the brain is likely to be; and the less glutamate is released relative to GABA, the smaller the 'disappointment' signal should be," said Steven Shabel, a postdoctoral student in Malinow's lab and the lead author of the new study.
    
Researchers studied rodents and found that the neurons of rodents with aspects of human depression produced less GABA relative to glutamate, compared with rodents without depression.
    
Also, when the animals with depression were given an antidepressant to raise their brains' serotonin levels, their relative GABA levels increased a sign that they were less disappointed after being denied their reward.     

"Our study suggests that one of the ways in which serotonin alleviates depression is by re-balancing the brain's processing of negative life events through the balance of glutamate and GABA in the habenula," Shabel said.
    
"We may now have a precise neurochemical explanation for why antidepressants make some people more resilient to negative experiences," he said.
    
Focusing on how to manipulate this newly discovered mechanism of competing neurotransmitters might be a promising avenue that leads to the discovery of a new generation of antidepressants, the researchers said.
    
The study was published in the journal Science.