Blood, adipose tissue and brain levels of the cannabinoid ligands WIN-55,212 and SR-141716A after their intraperitoneal injection in mice

Compound-specific and area-specific distribution within the brain

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cannabinoid ligands have wide ranging neural and behavioral effects; therefore, they are of substantial therapeutic interest. The levels of cannabinoids are tightly controlled in brain infusion and in vitro methodologies, although the studied dose-ranges are extremely wide (e.g. 0.4-470 nmol in brain infusion studies). The brain levels reached after systemic administration are virtually unknown. To investigate this issue, we injected intraperitoneally 3H-labeled WIN-55,212 and SR141716A (0.3, 1 and 3 mg/kg) and estimated their accumulation in the blood, adipose tissue and brain. Accumulation was dose-dependent. The largest amounts were found in the adipose tissue, while the levels seen in the blood and brain were approximately similar. The accumulation of SR141716A was markedly more pronounced than that of WIN-55,212 in all three tissues. The brain distribution of WIN-55,212 showed large regional differences. Such differences were significant but much smaller with SR141716A. The largest brain levels noticed after intraperitoneal injections did not exceed 2.5 nmol/g. This is larger than the brain level of the endocannabinoid anandamide but smaller than that of 2-arachidonoyl glycerol. Yet, the CB1 receptor affinity of WIN-55,212 and SR-141716A is two orders of magnitude larger than that of 2-arachidonoyl glycerol, suggesting that the exogenously administered compounds were functionally more active. Our findings also suggest that brain infusion and in vitro techniques employing considerably larger doses than 2.5 nmol should be dealt with caution. It appears that measuring brain levels after systemic injections increases our understanding of cannabinoid effects, and provides important clues for the comparison of results obtained with different methodologies.

Original languageEnglish
Pages (from-to)533-541
Number of pages9
JournalEuropean Neuropsychopharmacology
Volume19
Issue number8
DOIs
Publication statusPublished - Aug 2009

Fingerprint

rimonabant
Cannabinoids
Intraperitoneal Injections
Adipose Tissue
Ligands
Brain
Win 55212-2
Cannabinoid Receptor CB1
Endocannabinoids

Keywords

  • Brain
  • Concentration
  • Levels
  • Mice
  • SR-141716A
  • WIN-55,212

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Biological Psychiatry
  • Neurology
  • Pharmacology

Cite this

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title = "Blood, adipose tissue and brain levels of the cannabinoid ligands WIN-55,212 and SR-141716A after their intraperitoneal injection in mice: Compound-specific and area-specific distribution within the brain",
abstract = "Cannabinoid ligands have wide ranging neural and behavioral effects; therefore, they are of substantial therapeutic interest. The levels of cannabinoids are tightly controlled in brain infusion and in vitro methodologies, although the studied dose-ranges are extremely wide (e.g. 0.4-470 nmol in brain infusion studies). The brain levels reached after systemic administration are virtually unknown. To investigate this issue, we injected intraperitoneally 3H-labeled WIN-55,212 and SR141716A (0.3, 1 and 3 mg/kg) and estimated their accumulation in the blood, adipose tissue and brain. Accumulation was dose-dependent. The largest amounts were found in the adipose tissue, while the levels seen in the blood and brain were approximately similar. The accumulation of SR141716A was markedly more pronounced than that of WIN-55,212 in all three tissues. The brain distribution of WIN-55,212 showed large regional differences. Such differences were significant but much smaller with SR141716A. The largest brain levels noticed after intraperitoneal injections did not exceed 2.5 nmol/g. This is larger than the brain level of the endocannabinoid anandamide but smaller than that of 2-arachidonoyl glycerol. Yet, the CB1 receptor affinity of WIN-55,212 and SR-141716A is two orders of magnitude larger than that of 2-arachidonoyl glycerol, suggesting that the exogenously administered compounds were functionally more active. Our findings also suggest that brain infusion and in vitro techniques employing considerably larger doses than 2.5 nmol should be dealt with caution. It appears that measuring brain levels after systemic injections increases our understanding of cannabinoid effects, and provides important clues for the comparison of results obtained with different methodologies.",
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T1 - Blood, adipose tissue and brain levels of the cannabinoid ligands WIN-55,212 and SR-141716A after their intraperitoneal injection in mice

T2 - Compound-specific and area-specific distribution within the brain

AU - Barna, I.

AU - Till, I.

AU - Haller, J.

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N2 - Cannabinoid ligands have wide ranging neural and behavioral effects; therefore, they are of substantial therapeutic interest. The levels of cannabinoids are tightly controlled in brain infusion and in vitro methodologies, although the studied dose-ranges are extremely wide (e.g. 0.4-470 nmol in brain infusion studies). The brain levels reached after systemic administration are virtually unknown. To investigate this issue, we injected intraperitoneally 3H-labeled WIN-55,212 and SR141716A (0.3, 1 and 3 mg/kg) and estimated their accumulation in the blood, adipose tissue and brain. Accumulation was dose-dependent. The largest amounts were found in the adipose tissue, while the levels seen in the blood and brain were approximately similar. The accumulation of SR141716A was markedly more pronounced than that of WIN-55,212 in all three tissues. The brain distribution of WIN-55,212 showed large regional differences. Such differences were significant but much smaller with SR141716A. The largest brain levels noticed after intraperitoneal injections did not exceed 2.5 nmol/g. This is larger than the brain level of the endocannabinoid anandamide but smaller than that of 2-arachidonoyl glycerol. Yet, the CB1 receptor affinity of WIN-55,212 and SR-141716A is two orders of magnitude larger than that of 2-arachidonoyl glycerol, suggesting that the exogenously administered compounds were functionally more active. Our findings also suggest that brain infusion and in vitro techniques employing considerably larger doses than 2.5 nmol should be dealt with caution. It appears that measuring brain levels after systemic injections increases our understanding of cannabinoid effects, and provides important clues for the comparison of results obtained with different methodologies.

AB - Cannabinoid ligands have wide ranging neural and behavioral effects; therefore, they are of substantial therapeutic interest. The levels of cannabinoids are tightly controlled in brain infusion and in vitro methodologies, although the studied dose-ranges are extremely wide (e.g. 0.4-470 nmol in brain infusion studies). The brain levels reached after systemic administration are virtually unknown. To investigate this issue, we injected intraperitoneally 3H-labeled WIN-55,212 and SR141716A (0.3, 1 and 3 mg/kg) and estimated their accumulation in the blood, adipose tissue and brain. Accumulation was dose-dependent. The largest amounts were found in the adipose tissue, while the levels seen in the blood and brain were approximately similar. The accumulation of SR141716A was markedly more pronounced than that of WIN-55,212 in all three tissues. The brain distribution of WIN-55,212 showed large regional differences. Such differences were significant but much smaller with SR141716A. The largest brain levels noticed after intraperitoneal injections did not exceed 2.5 nmol/g. This is larger than the brain level of the endocannabinoid anandamide but smaller than that of 2-arachidonoyl glycerol. Yet, the CB1 receptor affinity of WIN-55,212 and SR-141716A is two orders of magnitude larger than that of 2-arachidonoyl glycerol, suggesting that the exogenously administered compounds were functionally more active. Our findings also suggest that brain infusion and in vitro techniques employing considerably larger doses than 2.5 nmol should be dealt with caution. It appears that measuring brain levels after systemic injections increases our understanding of cannabinoid effects, and provides important clues for the comparison of results obtained with different methodologies.

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