Phentermine induces conditioned rewarding effects via activation of the PI3K/Akt signaling pathway in the nucleus accumbens

Psychopharmacology
Sa-Ik HongChoon-Gon Jang

Abstract

Phentermine is structurally similar to methamphetamine and is widely used as an anti-obesity drug in the USA and many other countries. The potential for reward of phentermine has been noted; however, the mechanisms of phentermine dependence have not been established. Here, we investigated the rewarding and dopaminergic behavioral responses to phentermine in mice and found that phentermine produced conditioned rewarding effects through the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in the nucleus accumbens (NAc). The impact of phentermine was assessed using conditioned place preference (CPP) test, climbing behavior test, and western blot analysis. Phentermine 1 and 3 mg/kg (i.p.) significantly increased CPP. Phentermine, a known dopamine releaser, boosted apomorphine-induced climbing behavior in mice, and methamphetamine (i.p.) also increased apomorphine-induced dopaminergic behavior. Phentermine and methamphetamine increased the level of expression of the dopamine transporter (DAT) and phospho-Akt proteins to a similar degree in the NAc of CPP mice. To determine whether the conditioned rewarding effects of phentermine were mediated through the PI3K/Akt pathway, we assessed the effects of the Akt inhibitor LY294002 o...Continue Reading

References

Jan 1, 1988·Life Sciences·J ManzanaresF Zaragozá
Jul 21, 1998·Annals of the New York Academy of Sciences·R B RothmanM H Baumann
Jun 18, 2002·Journal of Neurochemistry·Lucia CarvelliAurelio Galli
Nov 19, 2002·Nature Neuroscience·Emanuela IzzoPietro Paolo Sanna
Jun 16, 2005·Progress in Neurobiology·David SulzerAurelio Galli
Jul 19, 2005·Physiology·Randy D BlakelyAurelio Galli
May 31, 2008·Biochemical and Biophysical Research Communications·Brandon J LuteAurelio Galli
Oct 22, 2008·Annual Review of Pharmacology and Toxicology·Jean-Martin BeaulieuMarc G Caron
Aug 28, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·George F Koob, Nora D Volkow
Aug 27, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sabrina D RobertsonAurelio Galli
Mar 22, 2012·Cellular Signalling·Marjelo A Mines, Richard S Jope
Dec 15, 2012·Cellular and Molecular Neurobiology·Tao LvJie Bai
Nov 19, 2013·Biomolecules & Therapeutics·Hye Jin ChaHo-Sang Jeong
Nov 22, 2014·Biomolecules & Therapeutics·Chang Soon ChoiGeon Ho Bahn
Dec 10, 2014·Biomolecules & Therapeutics·Hye Jin ChaHo-Sang Jeong
May 1, 1998·Annals of the New York Academy of Sciences·Richard B RothmanMichael H Baumann

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Citations

Nov 17, 2017·Nature Reviews. Neuroscience·Nora D VolkowRuben Baler
Dec 27, 2019·Current Drug Research Reviews·Nobue KitanakaJunichi Kitanaka
Jul 10, 2019·Frontiers in Cellular Neuroscience·Yanan LiChengbiao Lu

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