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.]).