The present address of Susana Mato is the Department of Neuroscience, University of the Basque Country, 48940 Leioa, Bizkaia, Spain.
CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors
Article first published online: 15 SEP 2007
Journal of Neurochemistry
Volume 103, Issue 5, pages 2111–2120, December 2007
How to Cite
Mato, S., Aso, E., Castro, E., Martín, M., Valverde, O., Maldonado, R. and Pazos, Á. (2007), CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. Journal of Neurochemistry, 103: 2111–2120. doi: 10.1111/j.1471-4159.2007.04961.x
- Issue published online: 15 SEP 2007
- Article first published online: 15 SEP 2007
- Received February 26, 2007; revised manuscript received August 2, 2007; accepted August 6, 2007.
- 5-HT1A receptors;
- 5-HT2A/2C receptors;
- CB1 receptors;
- [35S]GTPγS labelling;
- tail suspension test
Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioral and biochemical responses in CB1 receptor knockout mice. CB1 knockout animals exhibited a significant reduction in the induction of head twitches and paw tremor by the 5-HT2A/C receptor selective agonist (±) DOI, as well as a reduced hypothermic response following administration of the 5-HT1A receptor agonist (±)-8-OH-DPAT. Additionally, exposure to the tail suspension test induced enhanced despair responses in CB1 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 CB1 receptor knockout and wild-type mice. No differences were found between both genotypes with regard to 5-HT2A receptor and 5-HT1A receptors levels, measured by autoradiography in different brain areas. However, a significant decrease in the ability of both, the 5-HT1A receptor agonist (±)-8-OH-DPAT and the 5-HT2A/C receptor agonist (−)DOI, to stimulate [35S]GTPγS binding was detected in the hippocampal CA1 area and fronto-parietal cortex of CB1 receptor knockout mice, respectively. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A/C and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A and 5-HT2A receptors to G proteins might be involved in these effects.