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Front Behav Neurosci. 2015 Sep 3;9:235. doi: 10.3389/fnbeh.2015.00235. eCollection 2015.

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

Author information

1
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
2
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.
3
Department of Molecular Biology, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University Mannheim, Germany.

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.

KEYWORDS:

CB1 receptor; anxiety; raphe nuclei; serotonin; sociability

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