Cooperative regulation of anxiety and panic-related defensive behaviors in the rat periaqueductal grey matter by 5-HT1A and µ-receptors

• Published in: Journal of psychopharmacology (Oxford) 2013-12, Vol.27 (12), p.1141-1148
• Main Authors: Roncon, Camila M, Biesdorf, Carla, Coimbra, Norberto C, Audi, Elisabeth A, Zangrossi, Hélio, Graeff, Frederico G
• Format: Article
• Language: English
• Subjects: Animals; Anxiety - metabolism; Behavior, Animal - drug effects; Behavior, Animal - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Morphine - pharmacology; Naloxone - pharmacology; Neurons - metabolism; Panic - physiology; Panic Disorder - metabolism; Periaqueductal Gray - metabolism; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1A - drug effects; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Opioid, mu - drug effects; Receptors, Opioid, mu - metabolism; Serotonin - administration & dosage; Serotonin - metabolism; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881113485144

Previous results with the elevated T-maze (ETM) test indicate that the antipanic action of serotonin (5-HT) in the dorsal periaqueductal grey (dPAG) depends on the activation endogenous opioid peptides. The aim of the present work was to investigate the interaction between opioid- and serotonin-mediated neurotransmission in the modulation of defensive responses in rats submitted to the ETM. The obtained results showed that intra-dPAG administration of morphine significantly increased escape latency, a panicolytic-like effect that was blocked by pre-treatment with intra-dPAG injection of either naloxone or the 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1 piperazinyl] ethyl] -N- 2- pyridinyl-ciclohexanecarboxamide maleate (WAY-100635). In addition, previous administration of naloxone antagonized both the anti-escape and the anti-avoidance (anxiolytic-like) effect of the 5-HT1A agonist (±)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), but did not affect the anti-escape effect of the 5-HT2A agonist (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI). Moreover, the combination of sub-effective doses of locally administered 5-HT and morphine significantly impaired ETM escape performance. Finally, the µ-antagonist D-PHE-CYS-TYR-D-TRP-ORN-THR-PEN (CTOP) blocked the anti-avoidance as well as the anti-escape effect of 8-OHDPAT, and the association of sub-effective doses of the µ-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin acetate salt (DAMGO) and of 8-OHDPAT had anti-escape and anti-avoidance effects in the ETM. These results suggest a synergic interaction between the 5-HT1A and the µ-opioid receptor at post-synaptic level on neurons of the dPAG that regulate proximal defense, theoretically related to panic attacks.