New discovery could help nicotine addiction
28 Jan 2016 by Evoluted New Media
A lipid in brain cells may act as a switch, increasing or decreasing the need for motivation, a team of US scientists have announced.
A lipid in brain cells may act as a switch, increasing or decreasing the need for motivation, a team of US scientists have announced.
It is hoped the results of this trial could influence methods in the future to make it easier for people to quit smoking.
Professor Larry Parsons, senior author of the study, said: “We knew these lipids were implicated in nicotine addiction, but until now manipulating their synthesis was not pharmacologically feasible.”
Nicotine is known to affect neurons in the ventral tegmental area (VTA) - the reward centre in the brain - where motivation for rewards such as food, exercise and sex are found. This is achieved by inhibiting GABA’s (gamma aminobutyric acid), a neurotransmitter, inhibitory effect on excitatory signalling in the brain, while increasing the signalling of dopamine, an excitatory neurotransmitter.
Researchers from The Scripps Institute (TSRI) investigated whether compounds called 1,2,3-triazole urea (TU) inhibitors could block the production of a endocannabinoid, lipids released from nicotine activity on the brain. The specific endocannabinoid chosen was 2-arachidonoylglycerol (2-AG). TU inhibitors were researched to see if they could inhibit diacylglycerol, the enzyme responsible for the production of 2-AG.
In animal models with a history of nicotine exposure, GABA signalling returned to normal with the 1,2,3-TU inhibitors were used and also reduced the motivation to consume nicotine. Crucially, it reduced voluntary nicotine self-administration but did not change the effect of other natural rewards – such as a thirsty rat drinking water.
Matthew Buczynski, co-first author of the study, said: “This suggests 2-AG acts as a molecular switch for turning an important inhibitory control of dopamine neurons on and off.
“If this switch is turned off, as in those with chronic nicotine exposure, the excitation of dopamine neurons by nicotine is less controlled, and the drug is more rewarding,” he said.
