التفاصيل البيبلوغرافية
| العنوان: |
Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid 'Spice' compounds: comparison with Δ9 -tetrahydrocannabinol. |
| المؤلفون: |
Hoffman, Alexander F., Lycas, Matthew D., Kaczmarzyk, Jakub R., Spivak, Charles E., Baumann, Michael H., Lupica, Carl R. |
| المصدر: |
Addiction Biology; Mar2017, Vol. 22 Issue 2, p390-399, 10p |
| مصطلحات موضوعية: |
HIPPOCAMPUS physiology, TETRAHYDROCANNABINOL, NEURAL transmission, PSYCHIATRIC drugs, COMPARATIVE studies, THERAPEUTICS, GLUTAMIC acid metabolism, ANIMAL experimentation, CANNABIS (Genus), CELL receptors, DRUGS, GLUTAMIC acid, HIPPOCAMPUS (Brain), HYDROCARBONS, RESEARCH methodology, MEDICAL cooperation, MICE, NEUROPLASTICITY, NEUROTRANSMITTERS, RESEARCH, EVALUATION research, INDOLE compounds, PHARMACODYNAMICS |
| مستخلص: |
There has been a marked increase in the availability of synthetic drugs designed to mimic the effects of marijuana. These cannabimimetic drugs, sold illicitly as 'Spice' and related products, are associated with serious medical complications in some users. In vitro studies suggest that synthetic cannabinoids in these preparations are potent agonists at central cannabinoid CB1 receptors (CB1Rs), but few investigations have delineated their cellular effects, particularly in comparison with the psychoactive component of marijuana, Δ9 -tetrahydrocannabinol (Δ9 -THC). We compared the ability of three widely abused synthetic cannabinoids and Δ9 -THC to alter glutamate release and long-term potentiation in the mouse hippocampus. JWH-018 was the most potent inhibitor of hippocampal synaptic transmission (EC50 ~15 nM), whereas its fluoropentyl derivative, AM2201, inhibited synaptic transmission with slightly lower potency (EC50 ~60 nM). The newer synthetic cannabinoid, XLR-11, displayed much lower potency (EC50 ~900 nM) that was similar to Δ9 -THC (EC50 ~700 nM). The effects of all compounds occurred via activation of CB1Rs, as demonstrated by reversal with the selective antagonist/inverse agonist AM251 or the neutral CB1R antagonist PIMSR1. Moreover, AM2201 was without effect in the hippocampus of transgenic mice lacking the CB1R. Hippocampal slices exposed to either synthetic cannabinoids or Δ9 -THC exhibited significantly impaired long-term potentiation (LTP). We find that, compared with Δ9 -THC, the first-generation cannabinoids found in Spice preparations display higher potency, whereas a recent synthetic cannabinoid is roughly equipotent with Δ9 -THC. The disruption of synaptic function by these synthetic cannabinoids is likely to lead to profound impairments in cognitive and behavioral function. [ABSTRACT FROM AUTHOR] |
|
Copyright of Addiction Biology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder