Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.
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| Title: | Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. |
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| Authors: | Justinova, Zuzana, Mascia, Paola, Wu, Hui-Qiu, Secci, Maria E, Redhi, Godfrey H, Panlilio, Leigh V, Scherma, Maria, Barnes, Chanel, Parashos, Alexandra, Zara, Tamara, Fratta, Walter, Solinas, Marcello, Pistis, Marco, Bergman, Jack, Kangas, Brian D, Ferré, Sergi, Tanda, Gianluigi, Schwarcz, Robert, Goldberg, Steven R |
| Source: | Nature Neuroscience. Nov2013, Vol. 16 Issue 11, p1652-1661. 10p. |
| Subjects: | Cannabinoids, Neural circuitry, Disease relapse prevention, Nicotinic acetylcholine receptors, Squirrel monkeys, Animal models in research, Rats |
| Abstract: | In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ9-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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