Systemic administration of a nitric oxide synthase inhibitor impairs fear sensitization in the plus-maze

Abstract The aim of the present study was to evaluate the occurrence of fear sensitization in rats previously treated with an inhibitor of the NO syntheses and submitted to Trial1/Trial2 plus-maze (PM) procedure. Male Wistar rats received a systemic treatment with N ω -nitro- l -Arginine-methyl ester ( l -NAME; 5, 10 or 50 mg kg −1 ) and were submitted to PM Trial1. In the following day the animals were re-exposed to the PM with no drug administration (Trial2). Some standards spatial–temporal measures, such as the percentage of entries (% Open arm entries) and time spent (% Open arm time) in the open arms and risk assessment frequency were recorded and used to estimate the animal level of fear sensitization in PM Trial2. The results showed that animals receiving l -NAME (50 mg kg −1 ) displayed increased % Open arm entries and % Open arm time in Trial2 in relation to the group receiving 0.9% saline, which is compatible with impaired fear/anxiety acquisition during Trial1/Trial2 PM procedure. In addition, rats treated with l -NAME (50 mg kg −1 ) exhibited low level of risk assessment in Trial2 in relation to the group treated with 0.9% saline, which indicates low level of fear/anxiety during PM re-exposure. The number of entries into the enclosed arms was not changed by any l -NAME treatment, which suggests no bias of the drug treatments on animal locomotor activity. The data suggest that NO synthesis may mediate the fear sensitization process in the PM.