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AANS Neurosurgeon | Volume 26, Number 2, 2017


Flipping Molecular Switch May Reduce Nicotine’s Effects in the Brain

Scientists from The Scripps Research Institute recently discovered that a lipid in brain cells may act as a “switch” to increase or decrease the motivation to consume nicotine. The team’s findings in animal models point a way to a drug that might someday return this lipid to normal levels, potentially making it easier for smokers to quit. The degree to which the brain’s reward system can be activated is normally tightly controlled by the neurotransmitter GABA, which inhibits excitatory signaling in neurons and keeps the system in balance. However, chronic nicotine exposure sabotages this carefully balanced system. Previous research indicated that chronic nicotine exposure boosts the excitation of dopamine signaling while decreasing the controls on this system by GABA’s inhibitory signaling. The new study suggests compounds called 1,2,3-triazole urea (TU) inhibitors can block the production of a specific endocannabinoid called 2-arachidonoylglycerol (2-AG). These inhibitors were selected by researchers for their potential to inhibit the source of 2-AG itself — an enzyme called diacylglycerol lipase. During the study, researchers found that in animal models with a history of nicotine exposure, GABA signaling returned to normal when the effects of nicotine on 2-AG production were prevented with the 1,2,3-TU inhibitors. Blocking 2-AG production also affected the motivation to consume nicotine. Researchers observed that treating rats with the 1,2,3-TU inhibitors reduced voluntary nicotine self-administration without changing the motivation for natural rewards (water self-administration by thirsty rats). To read more about this study, click here.


2019 Mayo Clinic Advancements in Surgical & Medical Management of the Spine
Jan. 13-17, 2019; Kohala Coast, Big Island, Hawaii

Pituitary Education Day
Jan. 16-18, 2019; Orlando, Fla.

Innovations in Endoscopic Minimally Invasive Brain Surgery
Jan. 16-19, 2019; Celebration, Fla.

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