Involvement of endocannabinoids in antidepressant and anti-compulsive effect of fluoxetine in mice

► Role of eCBs in antidepressant and anti-compulsive effect of fluoxetine (FLX) was studied. ► Mouse model of forced swim test (FST) and marble-burying behavior (MBB) were employed. ► eCBs exhibited antidepressant effect in FST and produced ‘U’-shaped response curve in MBB. ► Co-joint injections of...

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Bibliographic Details
Published in:Behavioural brain research 2011-09, Vol.223 (1), p.125-134
Main Authors: Umathe, Sudhir N., Manna, Shyamshree S.S., Jain, Nishant S.
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
AM404
Anandamide
Animals
Antidepressive Agents - administration & dosage
Antidepressive Agents - pharmacology
Antidepressive Agents - therapeutic use
Anxiety disorders. Neuroses
Arachidonic Acids - administration & dosage
Arachidonic Acids - pharmacology
Behavioral psychophysiology
Benzamides - administration & dosage
Benzamides - pharmacology
Biological and medical sciences
Cannabinoid Receptor Modulators - administration & dosage
Cannabinoid Receptor Modulators - pharmacology
Cannabinoid Receptor Modulators - therapeutic use
Carbamates - administration & dosage
Carbamates - pharmacology
Compulsive Behavior - drug therapy
Depression - drug therapy
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Drug Therapy, Combination
Endocannabinoids
Fluoxetine - administration & dosage
Fluoxetine - pharmacology
Fluoxetine - therapeutic use
Fundamental and applied biological sciences. Psychology
Injections, Intraventricular
Male
Marble-burying behavior
Medical sciences
Mice
Motor Activity - drug effects
Motor Activity - physiology
Neuropharmacology
Obsessive-compulsive disorder
Obsessive-compulsive disorders
Pharmacology. Drug treatments
Piperidines - pharmacology
Polyunsaturated Alkamides - administration & dosage
Polyunsaturated Alkamides - pharmacology
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Psychopharmacology
Pyrazoles - pharmacology
Serotonin selective reuptake inhibitors
URB597
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Summary:► Role of eCBs in antidepressant and anti-compulsive effect of fluoxetine (FLX) was studied. ► Mouse model of forced swim test (FST) and marble-burying behavior (MBB) were employed. ► eCBs exhibited antidepressant effect in FST and produced ‘U’-shaped response curve in MBB. ► Co-joint injections of FLX and eCBs in subthreshold doses potentiated the effect on both the tests. ► CB 1 receptor antagonist blocked antidepressant and anti-compulsive effect of FLX. ► Indicating interplay between eCB and serotonergic system in depression and compulsive-like behavior. Endocannabinoid analogues exhibit antidepressant and anti-compulsive like effects similar to that of serotonin selective reuptake inhibitors (SSRIs) indicating a parallelism between the effects of serotonin and endocannabinoids. Therefore, the present study was designed to investigate the role of endocannabinoids in the antidepressant and anti-compulsive like effect of fluoxetine using mice model of forced swim test (FST) and marble-burying behavior (MBB). The results revealed that intracerebroventricular injections of endocannabinoid analogues, anandamide, a CB 1 agonist (AEA: 1–20 μg/mouse); AM404, an anandamide transport inhibitor (0.1–10 μg/mouse); and URB597, a fatty acid amide hydrolase inhibitor (0.05–10 μg/mouse) produced antidepressant-like effect dose-dependently, whereas influenced the MBB in a biphasic manner (produced a U-shaped dose–response curve). Fluoxetine (2.5–20 mg/kg, i.p.) dose dependently decreased the immobility time as well as burying behavior. Co-administration of sub-effective dose of fluoxetine (2.5 mg/kg, i.p.) potentiated the effect of sub-effective dose of AEA (0.5 μg/mouse, i.c.v.), AM404 (0.05 μg/mouse, i.c.v) or URB597 (0.01 μg/mouse, i.c.v) in both the paradigms. Interestingly, pretreatment with AM251, a CB 1 antagonist, blocked the effect of fluoxetine in FST and MBB at a dose (1 μg/mouse, i.c.v) that per se had no effect on either parameter. Similar effects were obtained with endocannabinoid analogues in AM251 pretreated mice. However, AM251 increased the burying behavior in MBB at a highest dose tested (5 μg/mouse). None of the treatments had any influence on locomotor activity. Thus, the study indicates an interaction between endocannabinoid and serotonergic system in regulation of depressive and compulsive-like behavior.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2011.04.031