Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors.
OBJECTIVE
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic- and antipsychotic-like effects in animal models. Effects of CBD may be mediated by the activation of 5-HT(1A) receptors. As 5-HT(1A) receptor activation may induce antidepressant-like effects, the aim of this work was to test the hypothesis that CBD would have antidepressant-like activity in mice as assessed by the forced swimming test. We also investigated if these responses depended on the activation of 5-HT(1A) receptors and on hippocampal expression of brain-derived neurotrophic factor (BDNF).


METHODS
Male Swiss mice were given (i.p.) CBD (3, 10, 30, 100 mg*kg(-1)), imipramine (30 mg*kg(-1)) or vehicle and were submitted to the forced swimming test or to an open field arena, 30 min later. An additional group received WAY100635 (0.1 mg*kg(-1), i.p.), a 5-HT(1A) receptor antagonist, before CBD (30 mg*kg(-1)) and assessment by the forced swimming test. BDNF protein levels were measured in the hippocampus of another group of mice treated with CBD (30 mg*kg(-1)) and submitted to the forced swimming test.


RESULTS
CBD (30 mg*kg(-1)) treatment reduced immobility time in the forced swimming test, as did the prototype antidepressant imipramine, without changing exploratory behaviour in the open field arena. WAY100635 pretreatment blocked CBD-induced effect in the forced swimming test. CBD (30 mg*kg(-1)) treatment did not change hippocampal BDNF levels.


CONCLUSIONS
CBD induces antidepressant-like effects comparable to those of imipramine. These effects of CBD were probably mediated by activation of 5-HT(1A) receptors.
Zanelati
T V
TV
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Biojone
C
C
Moreira
F A
FA
Guimarães
F S
FS
Joca
Sâmia R L
SR
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects / Q000378:metabolism; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D013550:Swimming
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D002185:Cannabidiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007099:Imipramine