Understanding addiction and its link to negative emotion

Despite human technology’s great medical advancement, the power to totally cure a person of addiction continues to elude scientists. This is evident by the fact that each year, the number of drug addicts, and worse still, the number of relapse cases, continues to rise in Malaysia.

Dr Satoshi Ogawa - Jeffrey Cheah School of Medicine and Health Sciences

“The main problem curing addiction begin with the difficulty of addicted individuals to break their addiction habits,” said Dr Satoshi Ogawa, lecturer of Physiology in Monash University Malaysia.

“Regardless of whether it is food addiction, internet addiction, sex addiction, drug addiction or smoking addiction, it is basically the same and addiction shares a common pathway,” he said.

To find a way to help addicts recover, one must first have a firm understanding of the mechanisms that lead to their addictions, said Dr Ogawa.

“When a person is exposed to something that he or she likes, such as food or sex and so on, the neurotransmitter, dopamine release in the brain’s pleasure centre, which makes people feel happy. Addictive drugs alter this motivational system,” he explained.

“All drugs of abuse, from nicotine to heroin, cause a particularly powerful surge of dopamine, so even without any of those “happy triggers”, dopamine levels will increase so it’s an instant way to feel good. Also, with drugs, the sensation is much more robust and heightened. This creates the addiction pathway.”

Dr Ogawa’s research is focused on the increasing occurrence of relapse cases for addicts who have stopped using drugs for a period of time, only to return to their old habits.

“For these former addicts, they no longer need the drugs as it has been out of their system for some time, but they will likely return to drug use. So why do they go back to drugs?”

Dr Ogawa’s research led him to focus on negative emotionality such as anxiety, sadness and fear triggered by exposure to stressful stimuli as one of the possible reasons for a relapse into drug-seeking behaviour. Dr Ogawa was keen to discover the link between the emotional stress and addiction.

Dr Ogawa has been focusing on the habenula, an evolutionarily conserved old brain structure.

“The habenula is known to play a major role in controlling serotonin, the neurotransmitter that plays key roles in the regulation of emotions, such as fear, anxiety, and depression.  In addition, the habenula neurons also signal to dopamine neurons when no reward is expected. Therefore, the habenula could be an important brain region linking negative emotions and addiction process.”

His foray into studying neural circuits linking negative emotions and addiction first kicked off years ago when he embarked on a research into the role of a specialised molecule called kisspeptin, in reproduction.

In the course of his research, Dr Ogawa discovered the potential role of kisspeptin and its receptor, Kiss-R in modulation of serotonin system in his fish models.

“Since the existence of Kiss-R in the habenula is also noted in mammalian brain, our finding suggests that the role of kisspeptin signalling in serotonin modulation could be evolutionarily conserved in vertebrates.”

“Our team was the first to ever discover the role of kisspeptin in non-reproductive function, and this discovery impacts many studies into human emotions,” he said.

His team is currently trying to understand the potential role of the kisspeptin in the dopaminergic system and its potential role in addiction.

Dr Ogawa said understanding of the potential role of kisspeptin system in addiction would be useful to understand the neural circuitry mediating drug abuse and emotional stress.

“If kisspeptin has been proven to be a mediator linking negative emotion and drug addiction, kisspeptin would be useful therapeutic agent/target for drug addiction through alteration of drug withdrawal associated with drug motivation,” he said.

Dr Ogawa, who obtained his PhD in Physiology from Nippon Medical School in Japan, said he believes his research into the role of kisspeptin and other molecules in the habenular will undoubtedly result in many more surprising discoveries.

Dr. Ogawa currently works with two research staff, four PhD and two Masters students. He has recently initiated a collaborative project with researchers  abroad such as Singapore and Japan to generate transgenic zebrafish that allows them to visualize whole-brain neural activity in real-time.

“There will be many things we can do with the discovery of pathways, and our ultimate aim will be to use our findings for improving the quality of life,” he said.