RESUMEN
BACKGROUND: Antidepressants are the first-choice for pharmacological treatment of panic disorder. However, they present disadvantages, such as delayed therapeutic effect, many side effects and a considerable rate of non-responders. These shortcomings prompt the development of new therapeutic strategies. Among these are the adjunctive use of enkephalinase inhibitors, such as opiorphin, which supposedly acts by increasing the availability of brain enkephalins and other endogenous opioids. AIMS: We here evaluated whether opiorphin in the dorsal periaqueductal grey matter (dPAG), a key panic-related area, accelerates and/or facilitates the antipanic-like effect of fluoxetine or imipramine. We also verified whether the panicolytic effect of imipramine depends on activation of µ-opioid receptors (MORs). METHODS: Male Wistar rats were submitted to the escape task of the elevated T-maze, an index of panic attack, after treatment with imipramine (3, 7 or 21 days) or fluoxetine (3, 7, 14 or 21 days), combined with an intra-dPAG injection of opiorphin. RESULTS: Opiorphin facilitated and accelerated the panicolytic-like effect caused by imipramine, but not with fluoxetine. The antipanic-like effect caused by chronic imipramine did not depend on MOR activation in the dPAG. CONCLUSION: Combined treatment of antidepressant drugs with opiorphin for hastening or potentiating the effects of the former compounds may not be generally effective, with the results varying depending on the type/class of these panicolytic drugs.