title: Cannabinoid type-1 receptor signaling in central serotonergic neurons regulates anxiety-like behavior and sociability.
abstract: The endocannabinoid (eCB) system possesses neuromodulatory functions by influencing the release of various neurotransmitters, including γ-aminobutyric acid (GABA) and glutamate. A functional interaction between eCBs and the serotonergic system has already been suggested. Previously, we showed that cannabinoid type-1 (CB1) receptor mRNA and protein are localized in serotonergic neurons of the raphe nuclei, implying that the eCB system can modulate serotonergic functions. In order to substantiate the physiological role of the CB1 receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic 5-hydroxytryptamine (5-HT) neuron-specific CB 1 receptor-deficient mice, using the Cre/loxP system with a tamoxifen-inducible Cre recombinase under the control of the regulatory sequences of the tryptophan hydroxylase 2 gene (TPH2-CreER (T2)), thus, restricting the recombination to 5-HT neurons of the central nervous system (CNS). Applying several different behavioral paradigms, we revealed that mice lacking the CB1 receptor in serotonergic neurons are more anxious and less sociable than control littermates. Thus, we were able to show that functional CB1 receptor signaling in central serotonergic neurons modulates distinct behaviors in mice.
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Häring
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Enk
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aparisi Rey
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Loch
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Inigo
authors.initials: I
authors.lastname: Ruiz de Azua
authors.affiliation: Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany ; Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Tillmann
authors.initials: T
authors.lastname: Weber
authors.affiliation: Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.
authors.forename: Dusan
authors.initials: D
authors.lastname: Bartsch
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Monory
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
keywords: CB1 receptor; anxiety; raphe nuclei; serotonin; sociability