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Preclinical evidence for the atypical antipsychotic-like profile of Cannabidiol: effect on the extracelullar levels of DA in the prefrontal cortex, and a 5-HT1A-mediated mechanism

Jessika Urbanavicius

  • Montevideo,
  • Uruguay
  • Jessika Urbanavicius ¹
  • , Neielly S Rodrigues ²
  • , Julieta Pomi ¹
  • , Ximena López ¹
  • , Francisco S Guimaraes ²
  • , Cecilia Scorza ¹
  • 1 Deparatment of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
  • 2 Department of Pharmacology, Medical School of Ribeirao Preto, University of Sao Paulo, Brazil

The phytocannabinoid Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has emerged as a potential atypical antipsychotic, which mechanism of action is currently under study. Among different brain targets, dopamine (DA) neurotransmission and the serotonin 5-HT1A receptors (5-HT1A-R) could be related to CBD antipsychotic actions. In the context of the collaboration among our research groups, we studied the local (0.2, 1 and 5 µM) or systemic (60 mg/kg/i.p.) effect of CBD on DA extracellular levels in the medial prefrontal cortex (mPFC) by the in vivo microdialysis technique in non-anaesthetized male adult rats. DA levels in artificial cerebrospinal fluid (aCSF) were collected (1.5 µl/min/20 min) and analyzed by HPLC-ED. The role of 5-HT1A-R was also evaluated through the systemic administration of WAY100635 (5-HT1A-R antagonist; 0.3 mg/kg/i.p.) before CBD i.p. injection. Results showed that CBD significantly increased DA levels 20 to 60 min after i.p. injection (60 % from baseline), and this effect was significantly prevented in WAY100635 pre-treated animals. Although in a lower and shorter magnitude, local infusion of only 1 µM CBD evoked a significant increase in prefrontal DA extracellular levels (20 to 40 min; 30 % from baseline). Overall, our results demonstrated a 5-HT1A-R-mediated mechanism in DA modulation induced by CBD and suggest the engaging of other brain regions than mPFC. This action could underlie the CBD atypical antipsychotic property.