title: Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.
abstract: Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant. Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic. In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol. To further investigate this latter effect, we tested whether CBD (15-60mg/kg) would attenuate the catalepsy and c-Fos protein expression in the dorsal striatum induced by haloperidol (0.6mg/kg). We also evaluated if these effects occur through the facilitation of 5-HT1A receptor-mediated neurotransmission. For this, male Swiss mice were treated with CBD and haloperidol systemically and then subjected to the catalepsy test. Independent groups of animals were also treated with the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). As expected, haloperidol induced catalepsy throughout the experiments, an effect that was prevented by systemic CBD treatment 30min before haloperidol administration. Also, CBD, administered 2.5h after haloperidol, reversed haloperidol-induced catalepsy. Haloperidol also increased c-Fos protein expression in the dorsolateral striatum, an effect attenuated by previous CBD administration. CBD effects on catalepsy and c-Fos protein expression induced by haloperidol were blocked by the 5-HT1A receptor antagonist. We also evaluated the effects of CBD (60nmol) injection into the dorsal striatum on haloperidol-induced catalepsy. Similar to systemic administration, this treatment reduced catalepsy induced by haloperidol. Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT1A receptors.
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: andreza_buzolin@hotmail.com.
authors.forename: Andreza B
authors.initials: AB
authors.lastname: Sonego
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Gomes
authors.affiliation: Department of Morphology, Physiology and Stomatology, Faculty of Odontology of Ribeirão Preto, University of São Paulo, Brazil; Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del Bel
authors.affiliation: Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, Brazil; Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimaraes
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D002185:Cannabidiol / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000633:toxicity; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D051379:Mice; D009465:Neuromuscular Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D009465:Neuromuscular Agents; D010879:Piperazines; D016760:Proto-Oncogene Proteins c-fos; D011725:Pyridines; D018490:Serotonin Agents; D044282:Receptor, Serotonin, 5-HT1A; D002185:Cannabidiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006220:Haloperidol
keywords: 5HT(1A) receptors; Cannabinoids; Catalepsy; Fos expression; Typical antipsychotics