A major hurdle for those trying to quit smoking are often the symptoms of nicotine withdrawal - tremor, anxiety, increase in appetite, irritability. The impact of these symptoms can be significantly lessened through the active substance of a class of drugs targeting diabetes. A team of Italian, Swedish and US researchers came to this excellent result working on laboratory animals and published a study on The Journal of Neuroscience.
"Pioglitazone" is the active substance of the drug which doctors have been prescribing for over 20 years to patients affected from type-2 diabetes. This drug targets the PPAR-g receptors (the gamma isoform of the peroxisome proliferator-activated receptor). Once activated, these receptors allows the tissues to be more insulin-receptive. Researchers have found that these receptors are also able to reduce the typical symptoms of nicotine withdrawal.
"This is a very interesting result especially for the repercussions it may hold on the treatment of nicotine addicts. There are many young patients that tend to underestimate the health damages of tobacco dependence" says one of the authors of the study, Patrizia Romualdi, pharmacologist and professor at the University of Bologna. "The results of this study will pave the way for future treatments addressing new therapeutic targets of tobacco addiction".
Nicotine and addiction
Smoking is one of the main causes of diseases and avoidable deaths: the World Health Organization estimates that smoke kills more than 7 million people every year.
People become addicted to cigarettes because of nicotine, which acts on the neuronal circuits controlling repetitive behaviours, motivation and the reward system, which is in charge of the positive feelings involving gratification. Whoever tries to quit smoking, therefore giving up nicotine, experiences symptoms such as tremors, anxiety, depression, increased appetite and irritability. These symptoms often act as a deterrent when quitting cigarettes.
A drug for withdrawal syndromes
Looking for a solution to this issue, researchers focused on the PPAR-g receptor, which is known for being targeted by pioglitazone, a drug treating diabetes. Indeed, not only PPAR-g receptors act as insulin sensitizers, they are also able, once activated, to combat alcohol and opiates addictions. Hence the idea of testing pioglitazone for lessening the symptoms of nicotine withdrawal. Researchers tested this active substance on lab rats and mice under different circumstances with promising results.
"The outcome of our study shows how activated PPAR-g receptors are able to prevent physical and affective symptoms of nicotine abstinence" explains Patrizia Romualdi. "Our researches report an increase in the PPAR-g receptors' gene expression in both the hippocampus and the amigdala. Administering pioglitazone in the hippocampus diminishes the physiological sypmptoms of nicotine abstinence, whereas the same in the amigala lessens its emotional consequences such as anxiety and irritability".
Thanks to this new information on neurobiological mechanisms regulating PPAR-g receptors while acting against nicotine addiction, researchers are confident that they will be able to help patients quit smoking by using some molecules which will act on that receptor.
The authors of the study
“Activation of PPARγ Attenuates the Expression of Physical and Affective Nicotine Withdrawal Symptoms through Mechanisms Involving Amygdala and Hippocampus Neurotransmission” is the title of this study published on The Journal of Neuroscience.
From the University of Bologna, Patrizia Romualdi, Francesca Caputi and Sanzio Cadeletti participated in this study. Moreover, researchers from the University of Camerino led by Professor Roberto Ciccocioppo, from Linköping University (Sweden) and Omeros Corporation (USA) also took part in the study.