Cannabidiol effects in the prepulse inhibition disruption induced by amphetamine.
BACKGROUND
The information processing appears to be deficient in schizophrenia. Prepulse inhibition (PPI), which measures the inhibition of a motor response by a weak sensory event, is considered particularly useful to understand the biology of information processing in schizophrenia patients. Drugs that facilitate dopaminergic neurotransmission such as amphetamine induce PPI disruption in human and rodents. Clinical and neurobiological findings suggest that the endocannabinoid system and cannabinoids may be implicated in the pathophysiology and treatment of schizophrenia. Cannabidiol (CBD), a non-psychotomimetic constituent of the Cannabis sativa plant, has also been reported to have potential as an antipsychotic.


OBJECTIVE
Our aim was to investigate if CBD pretreatment was able to prevent PPI disruption induced by amphetamine. Since one possible mechanism of CBD action is the facilitation of endocannabinoid-mediated neurotransmission through anandamide, we tested the effects of an anandamide hydrolysis inhibitor (URB597) in the amphetamine-induced PPI disruption.


METHODS
Male Swiss mice were treated with CBD systemic or intra-accumbens, or URB597 (systemic) prior to amphetamine and were exposed to PPI test.


RESULTS
Amphetamine (10 mg/kg) disrupted PPI while CBD (15-60 mg/kg) or URB597 (0.1-1 mg/kg) administered alone had no effect. Pretreatment with CBD attenuated the amphetamine-disruptive effects on PPI test after systemic or intra-accumbens administration. Similar effects were also found with the inhibitor of anandamide hydrolysis.


CONCLUSIONS
These results corroborate findings indicating that CBD induces antipsychotic-like effects. In addition, they pointed to the nucleus accumbens as a possible site of these effects. The increase of anandamide availability may be enrolled in the CBD effects.
Departamento de Morfologia, Estomatologia e Patologia Básica, Faculdade de Odontologia, Universidade de São Paulo, Ribeirão Preto, SP, 14049-904, Brasil.
J F C
JF
Pedrazzi
A C
AC
Issy
F V
FV
Gomes
F S
FS
Guimarães
E A
EA
Del-Bel
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002185:Cannabidiol / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects*; D065808:Prepulse Inhibition / Q000187:drug effects*; D013216:Reflex, Startle / Q000187:drug effects*
D001549:Benzamides; D002219:Carbamates; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D002185:Cannabidiol; D000661:Amphetamine