Olfactory fear conditioning paradigm in rats: effects of midazolam, propranolol or scopolamine

In rodents, fear conditioned responses are more pronounced toward olfactory stimulus, since olfaction is a dominant sense in these subjects. The present study was outlined to investigate if the association between coffee odor (CS1) and electrical footshock (US) would be an effective model for the study of fear-induced behavior and whether compounds used in humans for emotional-related disorders such as midazolam, propranolol, or scopolamine, applied during the different stages of fear conditioning (acquisition, consolidation and expression), affect the defensive responses to both, the olfactory CS1, and the context (CS2) where the CS1 had been presented (second order conditioning). The results revealed that five pairings between coffee odor (CS1) and electrical footshock (US) were able to elicit consistent defensive responses and a second order conditioning to the context (CS2). Midazolam (0.375-0.5 mg/kg; i.p.) treatment was able to interfere with the CS1-US association and with the consolidation of the aversive information. The propranolol (5-10 mg/kg; i.p.) treatment interfered with the CS1-US association, with the retention of fear memory and with the CS1-CS2 association. Propranolol also attenuated the expression of conditioned fear responses when applied before the CS1 test session. Scopolamine (0.6-1.2 mg/kg; i.p.) treatment impaired the acquisition of CS1-US and CS1-CS2 associations, and also disrupted the expression of conditioned fear responses when injected prior to the CS1 test session. These findings have pointed out the usefulness for the olfactory fear conditioning paradigm to investigate drug effects on the acquisition, consolidation and expression of fear conditioned responses.