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

• Published in: Behavioural brain research Vol. 223; no. 1; pp. 125 - 134
• Main Authors: Umathe, Sudhir N., Manna, Shyamshree S.S., Jain, Nishant S.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 30.09.2011; Elsevier
• 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; URB597; FAAH; SSRIs; DMSO; Serotonin selective reuptake inhibitors; CNS; MBB; 8-OH-DPAT; GTPγS; Marble-burying behavior; AM251; ANOVA; 5-HT 2A; Obsessive-compulsive disorder; 5-HT 2C; AEA; DOI; FST; TRPV1; CB 2; CB 1; Anandamide; OCD; 2-AG; GABA; i.c.v; AM404; 5-HT; Obsessive compulsive disorder; Psychotropic; Anxiety disorder; Reuptake inhibitor; Cannabinoid; Selective serotonin reuptake inhibitor; Endocannabinoid; Antidepressant agent; Behavior; Serotonin; Fluoxetine; Arachidonic acid derivatives; Rodentia; Vertebrata; Mammalia; Mouse; Animal; Compulsion; Neurotransmitter
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2011.04.031

► 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.