Some of the neurotransmitters in brain, the chemical messengers of neurons, play a key role in influencing different moods. While serotonin is believed to elevate the mood, the role of many others is not known.

Scientists from Centre for Cellular and Molecular Biology (CCMB) and the Indian Institute of Chemical Technology (IICT) have found two other neurotransmitters to be playing a key role in depression in a study conducted on mice. Serotonin-based anti-depressants were found to be ineffective in the long run although they worked in the initial stages, according to Arvind Kumar, lead scientist of the study, which was published recently in ‘Biological Psychiatry’, the journal of the Society for Biological Psychiatry.

Dr. Kumar said many current anti-depressant medications working on serotonin and monoamine targets require a long time to improve the condition, suggesting that these therapies could be operating sub-optimally.

With medications taking long time to show the effect on mood, many people suffer from suicidal tendencies. So there was an urgent need to examine the role of other neurotransmitters and develop newer fast-acting anti-depressants.

During the study, small mice were subjected to the bullying of larger aggressive mice and at the end of 10 days of this protocol they were tested for depression and many of them developed depression. The researchers conducted molecular and metabolic studies on the depressed mice. They focussed on Glutamate and Gamma-aminobutyric (GABA) acid, two major excitatory and inhibitory neurotransmitters, which are involved in many functions such as motor behaviour, cognition and emotion. They found that the activities of both the neurotransmitters were reduced in depression in the prefrontal cortex, a brain area critical for decision-making and involved in reward or pleasure response as well as in regulation of emotions.

It was found that at the metabolic level, the pathways of both the neurotransmitters were affected and at molecular level, the expression of two genes responsible for the pathways was reduced.

The findings would help in developing novel therapeutic approaches for the treatment of depression, Dr. Arvind Kumar added.