PMID- 14665974
OWN - NLM
STAT- MEDLINE
DCOM- 20040519
LR  - 20191108
IS  - 0955-8810 (Print)
IS  - 0955-8810 (Linking)
VI  - 14
IP  - 8
DP  - 2003 Dec
TI  - Antidepressant-like and anorectic effects of the cannabinoid CB1 receptor inverse 
      agonist AM251 in mice.
PG  - 573-82
AB  - Psychopathological disorders, and depression in particular, are strongly linked 
      to eating attitude in obese patients. The identification of cannabinoid CB1 
      receptors (CB1Rs) in areas of the central nervous system (CNS) that have been 
      implicated in regulation of mood and food intake suggests that these receptors 
      may mediate such a behavioral link. The goal of this study was to evaluate CB1R 
      modulation of antidepressant-like effects and food intake. For this purpose, 
      129/SVE and C57BL/6 male mice were acutely dosed intraperitoneally (i.p.) with 
      the CB1R inverse agonist AM251 (3-30 mg/kg) and tested, respectively, in the 
      tail-suspension test (TST) and in the forced-swim test (FST), which have been 
      used widely as tests sensitive to antidepressant compounds. Like the 
      antidepressant desipramine (DMI, 16 mg/kg), AM251 significantly reduced 
      immobility at 10 mg/kg in the TST and at 1 and 10 mg/kg in the FST. Such a 
      decrease of immobility was not accompanied by an increase in motor activity in 
      the open field, suggesting that occupancy of CB1R by AM251 induced 
      antidepressant-like effects. This was supported by two additional experiments. 
      First, the co-administration of the CB1R agonist CP55940, at a dose that did not 
      induce motor impairment or profound hypothermia (0.01 mg/kg), reversed effects of 
      AM251 in the TST. Secondly, effects of AM251 in the FST were absent in CB1R 
      knockout (KO) mice. In addition to an antidepressant-like effect, AM251 reduced 
      fasting-induced hyperphagia over a comparable dose range. Taken together, these 
      data suggest that regulation of mood and food intake might be obtained through 
      inverse agonism of CB1R.
FAU - Shearman, L P
AU  - Shearman LP
AD  - Department of Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA.
FAU - Rosko, K M
AU  - Rosko KM
FAU - Fleischer, R
AU  - Fleischer R
FAU - Wang, J
AU  - Wang J
FAU - Xu, S
AU  - Xu S
FAU - Tong, X S
AU  - Tong XS
FAU - Rocha, B A
AU  - Rocha BA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Antidepressive Agents)
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 3I4FA44MAI (AM 251)
SB  - IM
MH  - Affect/*drug effects
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Feeding Behavior/*drug effects
MH  - Infusions, Parenteral
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Activity
MH  - Piperidines/*pharmacology
MH  - Pyrazoles/*pharmacology
MH  - Receptor, Cannabinoid, CB1/*drug effects/genetics/*physiology
EDAT- 2003/12/11 05:00
MHDA- 2004/05/20 05:00
CRDT- 2003/12/11 05:00
PHST- 2003/12/11 05:00 [pubmed]
PHST- 2004/05/20 05:00 [medline]
PHST- 2003/12/11 05:00 [entrez]
AID - 10.1097/00008877-200312000-00001 [doi]
PST - ppublish
SO  - Behav Pharmacol. 2003 Dec;14(8):573-82. doi: 10.1097/00008877-200312000-00001.