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- Title
CB<sub>1</sub> knockout mice display impaired functionality of 5-HT<sub>1A</sub> and 5-HT<sub>2A/C</sub> receptors.
- Authors
Mato, Susana; Aso, Ester; Castro, Elena; Martín, Miquel; Valverde, Olga; Maldonado, Rafael; Pazos, Ángel
- Abstract
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.
- Subjects
SEROTONIN uptake inhibitors; ANTIDEPRESSANTS; G proteins; NEUROLOGIC manifestations of general diseases; NEUROTRANSMITTER uptake inhibitors
- Publication
Journal of Neurochemistry, 2007, Vol 103, Issue 5, p2111
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2007.04961.x