AUTHOR=Lutz Beat , Häring Martin , Enk Vanessa , Aparisi Rey Alejandro , Loch Sebastian , Ruiz De Azua Inigo , Monory Krisztina , Weber Tillmann , Bartsch Dusan 

TITLE=Cannabinoid type-1 receptor signaling in central serotonergic neurons regulates anxiety-like behavior and sociability

JOURNAL=Frontiers in Behavioral Neuroscience

VOLUME=9

YEAR=2015

URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2015.00235

DOI=10.3389/fnbeh.2015.00235

ISSN=1662-5153

ABSTRACT=<p>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 (CB<sub>1</sub>) 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 CB<sub>1</sub> receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic 5-hydroxytryptamine (5-HT) neuron-specific <italic>CB</italic><sub>1</sub> 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 (<italic>TPH2-CreER</italic><sup>T2</sup>), 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 CB<sub>1</sub> receptor in serotonergic neurons are more anxious and less sociable than control littermates. Thus, we were able to show that functional CB<sub>1</sub> receptor signaling in central serotonergic neurons modulates distinct behaviors in mice.</p>