Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice

Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice Several studies have shown a functional relationship between the endogenous cannabinoid and opioid systems. However, acute effects of Δ9‐tetrahydrocannabinol (THC) and physical dependence were not modified in knockout mice with single deletion of mu (MOR), delta (DOR) or kappa (KOR) opioid receptors. To further investigate the neurobiological basis of cannabinoid dependence, we have evaluated acute pharmacological responses, rewarding effects, tolerance and dependence to THC in double MOR/DOR knockout mice. Antinociception and hypolocomotion induced by acute THC administration remained unaffected, whereas the hypothermic effect was slightly attenuated in these double knockout mice. During chronic THC treatment, knockout mice developed slower tolerance to the hypothermic effect, but the development of tolerance to antinociceptive and hypolocomotor effects was unchanged. The rewarding properties of THC, measured in the conditioned place preference paradigm, were reduced in knockout mice. Interestingly, the somatic manifestations of THC withdrawal were also significantly attenuated in mutant mice, suggesting that a cooperative action of MOR and DOR is required for the entire expression of THC dependence. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Neuroscience Wiley

Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice

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Publisher
Wiley
Copyright
Copyright © 2003 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0953-816X
eISSN
1460-9568
D.O.I.
10.1046/j.1460-9568.2003.02409.x
Publisher site
See Article on Publisher Site

Abstract

Several studies have shown a functional relationship between the endogenous cannabinoid and opioid systems. However, acute effects of Δ9‐tetrahydrocannabinol (THC) and physical dependence were not modified in knockout mice with single deletion of mu (MOR), delta (DOR) or kappa (KOR) opioid receptors. To further investigate the neurobiological basis of cannabinoid dependence, we have evaluated acute pharmacological responses, rewarding effects, tolerance and dependence to THC in double MOR/DOR knockout mice. Antinociception and hypolocomotion induced by acute THC administration remained unaffected, whereas the hypothermic effect was slightly attenuated in these double knockout mice. During chronic THC treatment, knockout mice developed slower tolerance to the hypothermic effect, but the development of tolerance to antinociceptive and hypolocomotor effects was unchanged. The rewarding properties of THC, measured in the conditioned place preference paradigm, were reduced in knockout mice. Interestingly, the somatic manifestations of THC withdrawal were also significantly attenuated in mutant mice, suggesting that a cooperative action of MOR and DOR is required for the entire expression of THC dependence.

Journal

European Journal of NeuroscienceWiley

Published: Jan 1, 2003

References

  • The effects of cannabinoids on the brain
    Ameri, Ameri
  • Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice
    Martin, Martin; Ledent, Ledent; Parmentier, Parmentier; Maldonado, Maldonado; Valverde, Valverde

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