| Intrinsic effects of AM4113, a putative neutral CB1 receptor selective antagonist, on open-field behaviors in rats. | |
| | |
MedLine Citation:
|
PMID: 18640150 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
We examined open-field effects in rats of the cannabinoid 1 receptor (CB1R) agonist WIN55,212-2 (WIN; 3 mg/kg) and its interaction with the CB1R putative neutral antagonist AM4113 (0.3 to 3 mg/kg). Separate studies examined AM4113 alone (0.3 to 5.6 mg/kg). Unlike the CB1R antagonist rimonabant, in vitro (e.g., [Sink K.S., McLaughlin P.J., Wood J.A., Brown C., Fan P., Vemuri V.K., Pang Y., Olzewska T., Thakur G.A., Makriyannis A., Parker L.A., Salamone J.D. The novel cannabinoid CB(1) receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats. Neuropsychopharmacology 2008a; 33: 946-955.; Sink K.S., Vemuri V.K., Olszewska T., Makriyannis A., Salamone J.D. Cannabinoid CB1 antagonists and dopamine antagonists produce different effects on a task involving response allocation and effort-related choice in food-seeking behavior. Psychopharmacology (Berl) 2008b; 196: 565-574.]) AM4113 produced no change in cAMP accumulation (neutral antagonism vis-a-vis inverse agonism). Recorded behaviors were: ambulation, rearing, circling, latency, scratching, grooming, defecation, urination and vocalization/squeaking. WIN reduced ambulation and rearing; AM4113 completely (ambulation) or partially (rearing) antagonized these behaviors. WIN alone resulted in circling and an increased latency to leave the start area; effects blocked by AM4113. AM4113 increased scratching and grooming, effects attenuated but not abolished by WIN. AM4113 alone tended to reduce ambulation and rearing and had no effect on latency or circling. AM4113 alone increased scratching and grooming. Effects on defecation, urination and vocalization were non-significant. The open-field effects of AM4113 are similar to those reported for rimonabant in rats. Yet, unlike the inverse agonists rimonabant and AM251, the putative neutral CB1R antagonist AM4113 did not produce signs of nausea in ferrets and rats ([Chambers A.P., Vemuri V.K., Peng Y., Wood J.T., Olszewska T., Pittman Q.J., Makriyannis A., Sharkey K.A. A neutral CB1 receptor antagonist reduces weight gain in rat. Am J Physiol Regul Integr Comp Physiol 2007; 293: R2185-2193.; Sink K.S., McLaughlin P.J., Wood J.A., Brown C., Fan P., Vemuri V.K., Pang Y., Olzewska T., Thakur G.A., Makriyannis A., Parker L.A., Salamone J.D. The novel cannabinoid CB(1) receptor neutral antagonist AM4113 suppresses food intake and food-reinforced behavior but does not induce signs of nausea in rats. Neuropsychopharmacology 2008a; 33: 946-955.; Sink K.S., Vemuri V.K., Olszewska T., Makriyannis A., Salamone J.D. Cannabinoid CB1 antagonists and dopamine antagonists produce different effects on a task involving response allocation and effort-related choice in food-seeking behavior. Psychopharmacology (Berl) 2008b; 196: 565-574.]). |
| | |
Authors:
|
T U C Järbe; B J LeMay; T Olszewska; V K Vemuri; J T Wood; A Makriyannis |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-06-29 |
Journal Detail:
|
Title: Pharmacology, biochemistry, and behavior Volume: 91 ISSN: 0091-3057 ISO Abbreviation: Pharmacol. Biochem. Behav. Publication Date: 2008 Nov |
Date Detail:
|
Created Date: 2008-09-05 Completed Date: 2008-11-06 Revised Date: 2011-09-26 |
Medline Journal Info:
|
Nlm Unique ID: 0367050 Medline TA: Pharmacol Biochem Behav Country: United States |
Other Details:
|
Languages: eng Pagination: 84-90 Citation Subset: IM |
Affiliation:
|
Northeastern University, Center for Drug Discovery, 116 Mugar, 360 Huntington Ave., Boston, MA 02115, USA. t.jarbe@neu.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Behavior, Animal / drug effects* Benzoxazines / pharmacology Defecation / drug effects Dose-Response Relationship, Drug Grooming / drug effects Injections, Intraperitoneal Male Morpholines / pharmacology Motor Activity / drug effects* Naphthalenes / pharmacology Piperidines / pharmacology Pyrazoles / pharmacology* Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 / antagonists & inhibitors* Urination / drug effects Vocalization, Animal / drug effects |
| Grant Support | |
ID/Acronym/Agency:
|
DA 00253/DA/NIDA NIH HHS; DA 00493/DA/NIDA NIH HHS; DA 03801/DA/NIDA NIH HHS; DA 07215/DA/NIDA NIH HHS; DA 09064/DA/NIDA NIH HHS; DA 09158/DA/NIDA NIH HHS; K02 DA000253-13/DA/NIDA NIH HHS; K05 DA000493-07/DA/NIDA NIH HHS; P01 DA009158-10/DA/NIDA NIH HHS; R01 DA007215-13/DA/NIDA NIH HHS; R01 DA009064-16/DA/NIDA NIH HHS; R37 DA003801-21/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/AM4113; 0/Benzoxazines; 0/Morpholines; 0/Naphthalenes; 0/Piperidines; 0/Pyrazoles; 0/Receptor, Cannabinoid, CB1; 134959-51-6/Win 55212-2; 158681-13-1/rimonabant |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Desipramine blocks alcohol-induced anxiety- and depressive-like behaviors in two rat strains.
Next Document: Structural characterization of a water-soluble polysaccharide from the roots of Codonopsis pilosula ...