Nicotine, alternative 2D rendering of the molecular skeleton showing the 3D conformation of its ring at lowest energy in actual space. Credit: Public Domain

Stress is a major cause of relapses after people quit smoking. Worrying situations like money or relationship problems can affect neurotransmitter levels in the brain and cause former smokers to reach for a cigarette. Researchers reporting in ACS Pharmacology & Translational Science have now found that compounds that activate γ-aminobutyric acid (GABA) receptors in the brain can prevent rats from self-administering elevated nicotine levels under stressful conditions in an animal model of relapse.

GABA is an inhibitory neurotransmitter that decreases nerve signals in the brain. When a person is under stress, their GABA levels can drop, causing some neurons to become hyperactive. Using an animal model, Burt Sharp and colleagues wanted to find out whether administration of rat compounds that stimulate GABAA, a specific type of GABA receptor, to specific neurons known as the main basolateral amygdala output neurons, reduced the relapse of nicotine in rats under stressful conditions can.

In the animal model, the rats were taught to push a lever to self-administer nicotine. After one week, the animals were withdrawn from the nicotine for 8 days. To cause stress, the researchers locked the rats in a small space. After the rodents were released, the team injected one of three compounds known as positive allosteric modulators of GABAA or PAMs into a specific region of the brain of stressed rats and then gave them access to the nicotine-administering levers. Untreated stressed rats pressed the levers about 1.5 times more often than before the abstinence period, while rats treated with one of the PAMs reduced nicotine intake to levels observed in non-stressed rats before the abstinence period. If similar effects are confirmed in humans, novel, selective PAMs could be helpful in ameliorating the stress-related relapse in smoked tobacco, with potentially fewer side effects than GABA administration, the researchers say.

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More information:
Burt M. Sharp et al. Allosteric Modulation of GABAA Receptors in Basolateral Amygdala Rats Blocks Stress-Enhanced Recovering from Nicotine Self-Administering, ACS Pharmacology & Translational Science (2020). DOI: 10.1021 / acsptsci.0c00111 Provided by the American Chemical Society

Quote: Compounds Block Stress-Enhanced Nicotine Uptake in Rats (2020, November 11), accessed November 11, 2020 from

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