Propranolol As A Potential Adjunct To Exposure Therapy In The Treatment Of Pathological Fear Memory: An Animal Model
Clinical studies have shown that exposure therapy is effective in reducing abnormal fear memory such as in post-traumatic stress disorder (PTSD). The treatment, however, is limited and abnormal fear memory often recovers. Using an analogue of exposure therapy in rats—hereafter referred to as the brief exposure procedure—we investigated the extent to which the effectiveness of the brief exposure procedure in reducing retention of fear could be enhanced or impaired by the ß-adrenergic blocker propranolol, a drug used to treat PTSD. Male Long Evans rats underwent contextual fear conditioning followed 24 hr later by the brief exposure procedure; the next day the animals received a retention test. Contextual fear conditioning consisted of placing rats in a dark compartment for 120 sec followed by a single footshock; the brief exposure procedure, in contrast to the standard extinction procedure, consisted of confining the animals to the dark compartment for 30 sec in the absence of shock and removing them before an opportunity to recall fear developed to a significant degree; the retention test consisted of returning the animals to the dark compartment for 180 sec. Freezing behavior provided a measure of fear during the brief exposure and the subsequent retention test. Propranolol (4 mg/kg or 10 mg/kg) or saline was injected 20 min prior to the brief exposure procedure or was injected in the absence of the brief exposure procedure yielding a total of 6 groups. The doses of propranolol chosen were based on electrophysiological evidence from a previous study indicating that propranolol has opposing dose-dependent effects on amygdala (central nucleus, CeA) activity: a relatively high dose (10 mg/kg) increases CeA activity; a relatively low dose (4 mg/kg) suppresses spontaneous CeA activity. The results were as follows: 1) Neither the brief exposure procedure administered in the absence of propranolol nor propranolol (4 mg/kg or 10 mg/kg) administered in the absence of the brief exposure procedure affected retention of the fear memory. 2) Propranolol administered prior to the brief exposure affected freezing behavior in a dose-dependent manner: the CeA activity-suppressing dose (4 mg/kg) did not affect freezing behavior either during the brief exposure or during the retention test 24 hrs later; the CeA activity-increasing dose (10 mg/kg) increased freezing behavior and did so during both the brief exposure and the retention test 24 hrs later. In conclusion, the present results indicate that the efficacy of propranolol as an adjunct to exposure therapy may be dose-dependent and suggest the importance of minimizing amygdala activation and resulting fear during exposure therapy.
Society For Neuroscience 2016 Annual Meeting
November 12-16, 2016
San Diego, CA
Allen M. Schneider; P. E. Simson; Zoe C. Frank , '16; Nikhil Paladugu , '16; Victor A. Gomes , '17; Robert M. Abishek , '17; JeeHae Kang , '18; Chien He Wong , '16; E. Carr Everbach; and L. G. Kirby.
"Propranolol As A Potential Adjunct To Exposure Therapy In The Treatment Of Pathological Fear Memory: An Animal Model".