Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter μ-opioid receptors

• Published in: Neuropharmacology 2015-12, Vol.99, p.620-626
• Main Authors: Roncon, Camila Marroni, Almada, Rafael Carvalho, Maraschin, Jhonatan Christian, Audi, Elisabeth Aparecida, Zangrossi, Hélio, Graeff, Frederico Guilherme, Coimbra, Norberto Cysne
• Format: Article
• Language: English
• Subjects: 5-HT1A receptor; Analgesics, Opioid - pharmacology; Animals; Avoidance Learning - drug effects; Avoidance Learning - physiology; Catheters, Indwelling; Dorsal periaqueductal gray matter; Dose-Response Relationship, Drug; Elevated T-maze; Enkephalin, Ala-MePhe-Gly- - pharmacology; Escape Reaction - drug effects; Escape Reaction - physiology; Fluoxetine; Fluoxetine - pharmacology; Male; Microinjections; Narcotic Antagonists - pharmacology; Neuropsychological Tests; Panic; Periaqueductal Gray - drug effects; Periaqueductal Gray - metabolism; Psychotropic Drugs - pharmacology; Random Allocation; Rats, Wistar; Receptors, Opioid, mu - agonists; Receptors, Opioid, mu - antagonists & inhibitors; Receptors, Opioid, mu - metabolism; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; μ-opioid receptor
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2015.08.037

Previously reported results have shown that the inhibitory effect of fluoxetine on escape behavior, interpreted as a panicolytic-like effect, is blocked by pretreatment with either the opioid receptor antagonist naloxone or the 5-HT1A receptor (5-HT1A-R) antagonist WAY100635 via injection into the dorsal periaqueductal gray matter (dPAG). Additionally, reported evidence indicates that the μ-opioid receptor (MOR) interacts with the 5-HT1A-R in the dPAG. In the present work, pretreatment of the dPAG with the selective MOR blocker CTOP antagonized the anti-escape effect of chronic fluoxetine (10 mg/kg, i.p., daily, for 21 days), as measured in the elevated T-maze (ETM) test, indicating mediation of this effect by the MOR. In addition, the combined administration of sub-effective doses of the selective MOR agonist DAMGO (intra-dPAG) and sub-effective doses of chronic as well as subchronic (7 days) fluoxetine increased avoidance and escape latencies, suggesting that the activation of MORs may facilitate and accelerate the effects of fluoxetine. The current observation that MORs located in the dPAG mediate the anti-escape effect of fluoxetine may open new perspectives for the development of more efficient and fast-acting panic-alleviating drugs. •This study showed the involvement of MORs in the effects of fluoxetine in rats subjected to the ETM.•The MORs mediate the anti-escape effect of chronic fluoxetine.•The activation of MORs may facilitate and accelerate the effects of fluoxetine.