CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors.

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.

• 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)

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

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)