Lack of CB₁ receptor activity impairs serotonergic negative feedback

Serotonergic and endocannabinoid systems are important substrates for the control of emotional behaviour and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB₁ cannabinoid receptor impaired serotonergic negative...

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Bibliographic Details
Published in:Journal of neurochemistry 2009-05, Vol.109 (3), p.935-944
Main Authors: Aso, Ester, Renoir, Thibault, Mengod, Guadalupe, Ledent, Catherine, Hamon, Michel, Maldonado, Rafael, Lanfumey, Laurence, Valverde, Olga
Format: Article
Language:English
Subjects:
5-HT
5-HT1A
5-HT2C
5-HTT
5-HT₁A
5-HT₂C
Animals
Area Under Curve
Biochemistry
Biological and medical sciences
Cannabinoides
CB1 cannabinoid receptor
CB₁ cannabinoid receptor
Cell receptors
Cell structures and functions
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Citalopram - metabolism
Dose-Response Relationship, Drug
Efectes fisiològics
Emotions
Extracellular Fluid - drug effects
Extracellular Fluid - metabolism
Feedback, Physiological - drug effects
Feedback, Physiological - genetics
Feedback, Physiological - physiology
Fluoxetine - pharmacology
Fundamental and applied biological sciences. Psychology
Gene Expression - drug effects
Gene Expression - genetics
Hippocampus - drug effects
Hippocampus - metabolism
Male
Mice
Mice, Knockout
Microdialysis - methods
Molecular and cellular biology
Monoamines receptors (catecholamine, serotonine, histamine, acetylcholine)
Neurology
Neurons - drug effects
Neurons - physiology
Neurotransmitters
Prefrontal Cortex - cytology
Protein Binding - drug effects
Raphe Nuclei - cytology
Receptor, Cannabinoid, CB1 - deficiency
Receptor, Serotonin, 5-HT2C - metabolism
Receptors
Rodents
Serotonin - metabolism
Serotonin Plasma Membrane Transport Proteins - metabolism
Serotonin Uptake Inhibitors - pharmacology
Serotonina
Tritium - metabolism
Vertebrates: nervous system and sense organs
Online Access:Get full text
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Summary:Serotonergic and endocannabinoid systems are important substrates for the control of emotional behaviour and growing evidence show an involvement in the pathophysiology of mood disorders. In the present study, the absence of the activity of the CB₁ cannabinoid receptor impaired serotonergic negative feedback in mice. Thus, in vivo microdialysis experiments revealed increased basal 5-HT extracellular levels and attenuated fluoxetine-induced increase of 5-HT extracellular levels in the prefrontal cortex of CB₁ knockout compared with wild-type mice. These observations could be related to the significant reduction in the 5-HT transporter binding site density detected in frontal cortex and hippocampus of CB₁ knockout mice. The lack of CB₁ receptor also altered some 5-HT receptors related to the 5-HT feedback. Extracellular recordings in the dorsal raphe nucleus (DRN) revealed that the genetic and pharmacological blockade of CB₁ receptor induced a 5-HT₁A autoreceptor functional desensitization. In situ hybridization studies showed a reduction in the expression of the 5-HT₂C receptor within several brain areas related to the control of the emotional responses, such as the DRN, the nucleus accumbens and the paraventricular nucleus of the hypothalamus, whereas an over-expression was observed in the CA3 area of the ventral hippocampus. These results reveal that the lack of CB₁ receptor induces a facilitation of the activity of serotonergic neurons in the DRN by altering different components of the 5-HT feedback as well as an increase in 5-HT extracellular levels in the prefrontal cortex in mice.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2009.06025.x