Authors:
Campos AC, Ferreira FR, Guimarães FS.
Abstract:
Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that
follows a traumatic experience. Predator exposure promotes long-lasting
anxiogenic effect in rodents, an effect related to symptoms found in
PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of
Cannabis sativa with anxiolytic effects. The present study investigated
the anti-anxiety actions of CBD administration in a model of PTSD. Male
Wistar rats exposed to a predator (cat) received, 1 h later, singled or
repeated i.p. administration of vehicle or CBD. Seven days after the
stress animals were submitted to the elevated plus maze. To investigate
the involvement of 5HT1A receptors in CBD effects animals were
pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore
possible neurobiological mechanisms involved in these effects, 5HT1A
receptor mRNA and BDNF protein expression were measured in the
hippocampus, frontal cortex, amygdaloid complex and dorsal
periaqueductal gray. Repeated administration of CBD prevented
long-lasting anxiogenic effects promoted by a single predator exposure.
Pretreatment with WAY100635 attenuated CBD effects. Seven days after
predator exposure 5HT1A mRNA expression was up regulated in the frontal
cortex and hippocampus. CBD and paroxetine failed to prevent this
effect. No change in BDNF expression was found. In conclusion, predator
exposure promotes long-lasting up-regulation of 5HT1A receptor gene
expression in the hippocampus and frontal cortex. Repeated CBD
administration prevents the long-lasting anxiogenic effects observed
after predator exposure probably by facilitating 5HT1A receptors
neurotransmission. Our results suggest that CBD has beneficial potential
for PTSD treatment and that 5HT1A receptors could be a therapeutic
target in this disorder.