Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats

Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that induces anxiolytic-like effects similar to diazepam in animal models of innate aversive behavior. However, the effects of CBD contextual conditioned fear have not been studied. Therefore, the aim of this work was to compare the behavioral and cardiovascular effects of CBD and diazepam, a prototype anxiolytic, in animals submitted to a contextual conditioned fear paradigm. Male Wistar rats were submitted to a 10 min conditioning session (six footshocks, 2.5 mA, 3 s, delivered at pseudo-random intervals). The behavioral and cardiovascular responses to the context were measured 24 h later in a 10 min test session. Diazepam (2.5 mg/kg), FG-7142 (8 mg/kg), a benzodiazepine inverse agonist, or CBD (10 mg/kg) were administered i.p. before the test session. Conditioned rats submitted to the aversive context exhibited more freezing behavior and a larger increase in blood pressure and heart rate as compared to non-conditioned animals. These effects were attenuated by CBD and diazepam in the conditioned animals. These drugs did not have any effect in non-conditioned rats. FG-7142 treatment failed to change the behavioral and cardiovascular responses to the aversive context. In conclusion, the results suggest that CBD has anxiolytic-like properties similar to those of diazepam in a rat model of conditioned fear to context. (c) 2006 Elsevier B.V. All rights reserved.