Effects of the novel cannabinoid CB1 receptor antagonist PF 514273 on the acquisition and expression of ethanol conditioned place preference

Melanie M. Pina, Christopher Cunningham

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism. Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion. To evaluate the role of CB1 receptors in primary ethanol reward, the highly potent and selective novel CB1 antagonist 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyrazolo[3,4-f][1,4]oxazepin-8(5H)-one (PF 514273) was administered 30 min before place preference conditioning with a fixed dose of ethanol (acquisition). To evaluate the role of CB1 receptors in ethanol-conditioned reward, PF 514273 was administered 30 min before place preference testing (expression). Although PF 514273 reduced ethanol-stimulated and basal locomotor activity, it did not perturb the acquisition or expression of ethanol-induced CPP. Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms. Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.

Original languageEnglish (US)
Pages (from-to)427-431
Number of pages5
JournalAlcohol
Volume48
Issue number5
DOIs
StatePublished - 2014

Fingerprint

Cannabinoid Receptor Antagonists
Cannabinoid Receptor CB1
reward
Ethanol
antagonism
Reward
paradigm
conditioning
alcoholism
liability
Oral Administration
animal
2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyrazolo(3,4-f)(1,4)oxazepin-8(5H)-one
Consummatory Behavior
Eating
drug
Appetite Depressants
Inbred DBA Mouse
Locomotion
Alcoholism

Keywords

  • CB1
  • DBA/2J
  • Ethanol
  • Inbred mice
  • Locomotor activity
  • PF 514273
  • Place preference
  • Reward
  • Rimonabant
  • SR141716A

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neurology
  • Toxicology
  • Health(social science)

Cite this

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abstract = "The centrally expressed cannabinoid receptor (CB1) has been considered a potential therapeutic target in treating alcoholism. Though CB1 receptors have been shown to modulate primary and conditioned ethanol reward, much of this research employed animal models that require ethanol ingestion or oral routes of administration. This is problematic considering CB1 antagonist drugs have high anorectic liability and have been used clinically in the treatment of obesity. Therefore, the present study examined CB1 antagonism in DBA/2J mice using an unbiased ethanol-induced conditioned place preference (CPP) procedure, a paradigm that does not require ethanol ingestion. To evaluate the role of CB1 receptors in primary ethanol reward, the highly potent and selective novel CB1 antagonist 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(2,2-difluoropropyl)-6,7-dihydro-2H-pyrazolo[3,4-f][1,4]oxazepin-8(5H)-one (PF 514273) was administered 30 min before place preference conditioning with a fixed dose of ethanol (acquisition). To evaluate the role of CB1 receptors in ethanol-conditioned reward, PF 514273 was administered 30 min before place preference testing (expression). Although PF 514273 reduced ethanol-stimulated and basal locomotor activity, it did not perturb the acquisition or expression of ethanol-induced CPP. Results from the present study appear inconsistent with other studies that have demonstrated a role for CB1 antagonism in ethanol reward using oral administration paradigms. Our findings suggest that CB1 antagonism may have greater involvement in consummatory behavior than ethanol reward.",
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AU - Cunningham, Christopher

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