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

Mato, Susana; Aso Pérez, Ester; Castro, Elena; Martín, Miguel; Valverde Granados, Olga; Maldonado, Rafael, 1961-; Pazos, Ángel

doi:http://dx.doi.org/10.1111/j.1471-4159.2007.04961.x

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

Citation

Mato S, Aso E, Castro E, Martín M, Valverde O, Maldonado R et al. CB1 knockout mice display impaired functionality of 5-HT1A and 5-HT2A/C receptors. J Neurochem. 2007;103:2111–20. DOI: 10.1111/j.1471-4159.2007.04961.x

Abstract

Interaction between brain endocannabinoid (EC) and serotonin (5-HT) systems was investigated by examining 5-HT-dependent behavioural 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 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 the 5-HT1A receptor agonist (±)-8-OH-DPAT to stimulate 35SGTPS binding was detected in the hippocampal CA1 area of CB1 receptor knockout mice. This study provides evidence that CB1 receptors are involved in the regulation of serotonergic responses mediated by 5-HT2A and 5-HT1A receptors, and suggests that a reduced coupling of 5-HT1A receptors to Gi/o proteins in the hippocampus might be involved in these effects.