The compounds block stress-enhanced nicotine reacquisition in rats

November 11, 2020

Stress is a major cause of relapse after people quit smoking. Worrying situations, such as money or relationship problems, can affect the levels of neurotransmitters in the brain, leading former smokers to take a cigarette. Now, the researchers who report ACS Pharmacology & Translational Science found that compounds that activate γ-aminobutyric acid (GABA) receptors in the brain can prevent rats from self-administering increased levels of nicotine during stressful conditions in an animal model of relapse.

GABA is an inhibitory neurotransmitter that reduces nerve signaling in the brain. When a person experiences stress, their GABA levels can decrease, causing some neurons to become overactive. Using an animal model, Burt Sharp and colleagues wanted to find out whether to give rats compounds that stimulate GABA_A, a specific type of GABA receptor on some neurons, called the main output neurons of the basolateral amygdala, could reduce the relapse of nicotine rats during stressful conditions.

In the animal model, rats were taught to press a lever to administer nicotine themselves. After one week, the animals were withdrawn from nicotine for 8 days. To cause stress, the researchers confined the rats to a small space. After releasing the rodents, the team injected one of three compounds, called GABA positive allosteric modulators._A, or PAM, in a specific brain region of the stressed rats, and thus gave them access to the nicotine delivery levers. Untreated stressed rats pressed the levers approximately 1.5 times more frequently than before the abstinence period, while rats treated with any of the MAPs reduced nicotine intake to levels observed in non-stressed rats before the period. of abstinence. If similar effects are confirmed in humans, new selective PAMs could be useful in alleviating the stress-induced relapse of smoking tobacco, with potentially fewer side effects than administering GABA, the researchers say.