Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors

• Published in: Behavioural brain research 2010-12, Vol.213 (2), p.225-229
• Main Authors: Soares, Vanessa de Paula, Campos, Alline Cristina, Bortoli, Valquíria Camin de, Zangrossi, Hélio, Guimarães, Francisco Silveira, Zuardi, Antonio Waldo
• Format: Article
• Language: English
• Subjects: 5-HT1A; Adult and adolescent clinical studies; Animals; Anxiety; Anxiety disorders. Neuroses; Behavioral psychophysiology; Biological and medical sciences; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - pharmacology; Cannabis sativa; dPAG; Electric Stimulation; Electrical stimulation; Elevated T-maze; Fundamental and applied biological sciences. Psychology; Male; Maze Learning - drug effects; Maze Learning - physiology; Medical sciences; Microinjections; Models, Animal; Panic; Panic - drug effects; Panic - physiology; Panic disorder; Periaqueductal Gray - drug effects; Periaqueductal Gray - physiology; Piperazines - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopathology. Psychiatry; Pyridines - pharmacology; Rats; Rats, Wistar; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.05.004

Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors.