title: Conditional cannabinoid receptor type 1 mutants reveal neuron subpopulation-specific effects on behavioral and neuroendocrine stress responses.
abstract: The complete genetic loss or pharmacological blockade of cannabinoid receptor type 1 (CB1) in mice results in both altered behavioral performance and increased stress hormone secretion in response to stressful encounters such as forced swim test (FST) exposure. CB1 is expressed on nerve terminals belonging to different neurotransmitter systems, including the glutamatergic and GABAergic system, where it is able to suppress excitatory and inhibitory neurotransmission, respectively. In the current study, we used the conditional mutagenesis approach in mice to investigate the neurotransmitter systems involved in these behavioral and neuroendocrine phenotypes in regard to CB1 signaling. Mice lacking CB1 in cortical glutamatergic neurons (Glu-CB1(-/-)) showed decreased passive stress coping (decreased immobility) in the FST, whereas mice lacking CB1 in principal forebrain neurons (CaMK-CB1(-/-)) and GABAergic neurons (GABA-CB1(-/-)), respectively, behaved as littermate controls. However, we found increased FST-induced corticosterone secretion only in CaMK-CB1(-/-) mice, whereas Glu-CB1(-/-) and GABA-CB1(-/-) mice exhibited normal corticosterone release as compared to controls. Thus, behavioral and neuroendocrine acute stress coping in response to the FST is mainly influenced by CB1 signaling on different glutamatergic neuronal subpopulations, but not by CB1 on GABAergic neurons.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. michel.steiner@actelion.com
authors.forename: Michel A
authors.initials: MA
authors.lastname: Steiner
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Carsten T
authors.initials: CT
authors.lastname: Wotjak
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D005971:Glutamates / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009490:Neurosecretory Systems / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D016548:Prosencephalon / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism; D013550:Swimming; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005971:Glutamates; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid; D003345:Corticosterone