Effects of AM1346, a high-affinity CB1 receptor selective anandamide analog, on open-field behavior in rats.
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.
Järbe
Torbjörn U C
TU
Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA. t.jarbe@neu.edu
DiPatrizio
Nicholas V
NV
Li
Chen
C
Makriyannis
Alexandros
A
D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003672:Defecation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology; D054314:Drug Inverse Agonism; D005106:Exploratory Behavior / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000502:physiology; D000077285:Rimonabant; D013239:Stereotyped Behavior / Q000187:drug effects; D014828:Vocalization, Animal / Q000187:drug effects
C517735:AM-1346; D001095:Arachidonic Acids; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; D013759:Dronabinol; D000077285:Rimonabant