TY - JOUR
T1 - Interaction between cannabinoid compounds and diazepam on anxiety-like behaviour of mice
AU - Naderi, Nima
AU - Haghparast, Abbas
AU - Saber-Tehrani, Ali
AU - Rezaii, Neguine
AU - Alizadeh, Amir Mohammad
AU - Khani, Abbas
AU - Motamedi, Fereshteh
N1 - Funding Information:
This work was supported by a grant from Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences (grant No. 307/A/A). We thank B. Shafaghi PhD for help with designing isobolographic analysis.
PY - 2008/3
Y1 - 2008/3
N2 - Previous studies have suggested that cannabinoidergic system is involved in anxiety. However, a complete picture of cannabinoid association in the anxiety is still lacking. In the present study, we investigated the possible interaction between cannabinoidergic and GABAergic systems in the anxiety-like behaviour of mice. Intraperitoneal (i.p.) administration of the cannabinoid receptor agonist WIN55212-2 (0.25-5 mg/kg), the endocannabinoid transport inhibitor AM404 (0.25-2 mg/kg) and diazepam (0.25-8 mg/kg) dose dependently exhibited an anxiolytic effect evaluated in terms of increase in the percentage of time spent in the open arms in the elevated plus maze (EPM) test. Administration of certain fixed-ratio combinations (3:1 and 1:1) of WIN55212-2 and diazepam produced a synergistic anxiolytic effect, while the 1:3 combination produced an additive effect. In hole-board test, administration of certain ratios of WIN55212-2-diazepam combination significantly altered the animal behaviour compared to groups that received each drug alone. Co-administration of AM404 (1 and 2 mg/kg) and diazepam (0.5 mg/kg) abolished the anxiolytic effect of the former drug in EPM and the latter in hole-board test, respectively. The combination of an ineffective dose of the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3 mg/kg, i.p.) on anxiety-related responses with an ineffective dose of diazepam (0.25 mg/kg, i.p.) led to a synergistic effect. Co-administration of the CB1 receptor antagonist, AM251 (5 mg/kg) and an effective dose of diazepam (2 mg/kg, i.p.) attenuated diazepam-induced elevation of percentage of time spent in open arm, while lower dose of AM251 (0.5 mg/kg) failed to inhibit diazepam-induced anxiolytic effect. Taken together, the present study showed that co-administration of exogenous cannabinoids and diazepam produce additive or synergistic effect at different combinations. Moreover, it has been shown that enhancement of the function of endocannabinoids could increase the anxiolytic effect of diazepam.
AB - Previous studies have suggested that cannabinoidergic system is involved in anxiety. However, a complete picture of cannabinoid association in the anxiety is still lacking. In the present study, we investigated the possible interaction between cannabinoidergic and GABAergic systems in the anxiety-like behaviour of mice. Intraperitoneal (i.p.) administration of the cannabinoid receptor agonist WIN55212-2 (0.25-5 mg/kg), the endocannabinoid transport inhibitor AM404 (0.25-2 mg/kg) and diazepam (0.25-8 mg/kg) dose dependently exhibited an anxiolytic effect evaluated in terms of increase in the percentage of time spent in the open arms in the elevated plus maze (EPM) test. Administration of certain fixed-ratio combinations (3:1 and 1:1) of WIN55212-2 and diazepam produced a synergistic anxiolytic effect, while the 1:3 combination produced an additive effect. In hole-board test, administration of certain ratios of WIN55212-2-diazepam combination significantly altered the animal behaviour compared to groups that received each drug alone. Co-administration of AM404 (1 and 2 mg/kg) and diazepam (0.5 mg/kg) abolished the anxiolytic effect of the former drug in EPM and the latter in hole-board test, respectively. The combination of an ineffective dose of the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (0.3 mg/kg, i.p.) on anxiety-related responses with an ineffective dose of diazepam (0.25 mg/kg, i.p.) led to a synergistic effect. Co-administration of the CB1 receptor antagonist, AM251 (5 mg/kg) and an effective dose of diazepam (2 mg/kg, i.p.) attenuated diazepam-induced elevation of percentage of time spent in open arm, while lower dose of AM251 (0.5 mg/kg) failed to inhibit diazepam-induced anxiolytic effect. Taken together, the present study showed that co-administration of exogenous cannabinoids and diazepam produce additive or synergistic effect at different combinations. Moreover, it has been shown that enhancement of the function of endocannabinoids could increase the anxiolytic effect of diazepam.
KW - Anxiety
KW - Cannabinoids
KW - Diazepam
KW - Elevated plus maze
KW - GABA
KW - Hole-board
KW - Mice
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U2 - 10.1016/j.pbb.2007.11.001
DO - 10.1016/j.pbb.2007.11.001
M3 - Article
C2 - 18096213
AN - SCOPUS:38049141701
SN - 0091-3057
VL - 89
SP - 64
EP - 75
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -