Abstract |
Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioral and biochemical responses in CB(1) receptor knockout mice. CB(1) knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT(2A/C) receptor selective agonist (+/-) DOI, as well as a reduced hypothermic response following administration of the 5-HT(1A) receptor agonist (+/-)-8- OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB(1) knockout mice. However, the tricyclic antidepressant imipramine and the 5-HT selective reuptake inhibitor fluoxetine induced similar decreases in the time of immobility in the tail suspension test in CB(1) receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT(2A) receptor and 5-HT(1A) receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of both, the 5-HT(1A) receptor agonist (+/-)-8- OH-DPAT and the 5-HT(2A/C) receptor agonist (-)DOI, to stimulate [(35)S] GTPgammaS binding was detected in the hippocampal CA(1) area and fronto-parietal cortex of CB(1) receptor knockout mice, respectively. This study provides evidence that CB(1) receptors are involved in the regulation of serotonergic responses mediated by 5-HT(2A/C) and 5-HT(1A) receptors, and suggests that a reduced coupling of 5-HT(1A) and 5-HT(2A) receptors to G proteins might be involved in these effects.
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Authors | Susana Mato, Ester Aso, Elena Castro, Miquel Martín, Olga Valverde, Rafael Maldonado, Angel Pazos |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 103
Issue 5
Pg. 2111-20
(Dec 2007)
ISSN: 1471-4159 [Electronic] England |
PMID | 17944876
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amphetamines
- Receptor, Cannabinoid, CB1
- Receptor, Serotonin, 5-HT2A
- Receptor, Serotonin, 5-HT2C
- Serotonin Receptor Agonists
- Receptor, Serotonin, 5-HT1A
- Guanosine 5'-O-(3-Thiotriphosphate)
- 8-Hydroxy-2-(di-n-propylamino)tetralin
- 4-iodo-2,5-dimethoxyphenylisopropylamine
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Topics |
- 8-Hydroxy-2-(di-n-propylamino)tetralin
(pharmacology)
- Amphetamines
(pharmacology)
- Animals
- Autoradiography
(methods)
- Behavior, Animal
(drug effects)
- Body Temperature
(drug effects, genetics)
- Female
- Gene Expression Regulation
(genetics)
- Guanosine 5'-O-(3-Thiotriphosphate)
(pharmacology)
- Mice
- Mice, Knockout
- Protein Binding
(drug effects)
- Receptor, Cannabinoid, CB1
(deficiency)
- Receptor, Serotonin, 5-HT1A
(genetics, metabolism)
- Receptor, Serotonin, 5-HT2A
(genetics, metabolism)
- Receptor, Serotonin, 5-HT2C
(genetics, metabolism)
- Serotonin Receptor Agonists
(pharmacology)
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