title: Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice.
abstract: Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans. It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson's patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders. To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms. The catalepsy test is largely used to investigate impairments of motor function caused by interference on striatal function. Male Swiss mice received acute pretreatment with CBD (5, 15, 30 or 60mg/kg, ip) 30min prior to the D2 receptor antagonist haloperidol (0.6mg/kg), the non-selective nitric oxide synthase (NOS) inhibitor L-nitro-N-arginine (L-NOARG, 80mg/kg) or the CB1 receptor agonist WIN55,212-2 (5mg/kg). The mice were tested 1, 2 or 4h after haloperidol, L-NOARG or WIN55,212-2 injection. These drugs significantly increased catalepsy time and this effect was attenuated dose-dependently by CBD. CBD, by itself, did not induce catalepsy. In a second set of experiments the mechanism of CBD effects was investigated. Thirty minutes before CBD (30mg/kg) the animals received the 5-HT1A receptor antagonist WAY100635 (0.1mg/kg). The anticataleptic effect of CBD was prevented by WAY100635. These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, SP, 14049-900, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil. Electronic address: gomesfv@usp.br.
authors.forename: Felipe V
authors.initials: FV
authors.lastname: Gomes
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del Bel
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D018492:Dopamine Antagonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*
chemical_list: D018492:Dopamine Antagonists; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D002185:Cannabidiol; D019001:Nitric Oxide Synthase
keywords: 5-HT1A receptor; CBD; Cannabidiol; Cannabinoids; Catalepsy test; L-NOARG; L-nitro-N-arginine; NO; NOS; Striatal disorders; cannabidiol; nitric oxide; nitric oxide sinthase; Δ(9)-THC; Δ(9)-tetrahydrocannabinol