کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
319034 | 539224 | 2009 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: CB1 receptor knockout mice are hyporesponsive to the behavior-stimulating actions of d-amphetamine: Role of mGlu5 receptors CB1 receptor knockout mice are hyporesponsive to the behavior-stimulating actions of d-amphetamine: Role of mGlu5 receptors](/preview/png/319034.png)
Blockade of the cannabinoid CB1 receptors (CB1R) has been shown to reduce psychostimulant-induced hyperactivity, an effect that we sought to further characterize here. The CB1R antagonist SR141716A dose-dependently decreased d-amphetamine-induced hyperactivity. Also, d-amphetamine-induced hyperlocomotion was reduced in CB1R knockout (KO) mice. However, CB1R KO and wild-type mice showed a similar d-amphetamine-induced increase in nucleus accumbens DA release. Hence, we investigated whether CB1R antagonism/invalidation reduces d-amphetamine-induced hyperlocomotion through a mechanism involving changes in glutamatergic neurotransmission. Blockade of metabotropic-glutamate-receptors-5 (mGluR5) with MPEP, but not blockade of N-methyl-d-aspartate-receptors (NMDA) with MK-801, restored to a great extent the blunted d-amphetamine-induced hyperlocomotion seen after CB1R antagonism/invalidation. Thus, hyporesponsiveness to the psychostimulant effects of d-amphetamine as a result of CB1R antagonism/invalidation is not due to an ensuing decrease in d-amphetamine-induced DA release in the nucleus accumbens, but rather due to a hyperglutamatergic state and facilitation of glutamatergic neurotransmission at the mGlu5, but not NMDA, receptors.
Journal: European Neuropsychopharmacology - Volume 19, Issue 3, March 2009, Pages 196–204