Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats

Behav Pharmacol. 2007 Nov;18(7):673-80. doi: 10.1097/FBP.0b013e3282f00bbf.

Abstract

AM1346 is a cannabinoid receptor type 1 (CB1R) anandamide analog [alkoxyacid amide of N-eicosa-(5Z, 8Z, 11Z, 14Z)-tetraenylamine] with high affinity and selectivity for the CB1 vs. CB2 receptor [Ki (CB1)=1.5 nmol/l; Ki (CB2)=152 nmol/l]. The present study characterized the effects of AM1346 (5.6-18 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR141716 (1-5.6 mg/kg) on open-field behaviors of rats. AM1346 reduced ambulation (horizontal activity), rearing (vertical activity) and increased the degree of circling and the latency to leave the central area of the open-field arena. AM1346 also tended to reduce defecation and to increase vocalization in a dose-dependent manner. In pretreatment studies, SR141716 completely blocked the effects of AM1346 on circling and latency and partially antagonized the effects of 18 mg/kg AM1346 on ambulation and rearing. SR141716 also tended to decrease AM1346-induced vocalization in a dose-dependent manner. Earlier studies have shown that SR141716, given alone, can increase grooming behavior and, as well, produces dose-related increases in scratching. In the present studies, these effects were attenuated in a dose-related manner by AM1346. The present profile of behavioral effects for AM1346 is consistent with its designation as a CB1R agonist. When combined with drug discrimination data (surmountable antagonism of effects of SR141716 by Delta(9)-THC and AM1346 but not by methanandamide, i.e. AM356), these data indicate that the anandamide analog AM1346 may be more behaviorally similar to cannabinoids like Delta(9)-THC than to other anandamide-based molecules such as methanandamide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arachidonic Acids / administration & dosage
  • Arachidonic Acids / pharmacology*
  • Behavior, Animal / drug effects*
  • Defecation / drug effects
  • Dose-Response Relationship, Drug
  • Dronabinol / pharmacology
  • Drug Inverse Agonism
  • Exploratory Behavior / drug effects
  • Grooming / drug effects
  • Male
  • Motor Activity / drug effects
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / administration & dosage
  • Polyunsaturated Alkamides / pharmacology*
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB1 / physiology
  • Rimonabant
  • Stereotyped Behavior / drug effects
  • Vocalization, Animal / drug effects

Substances

  • AM-1346
  • Arachidonic Acids
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • methanandamide
  • Dronabinol
  • Rimonabant