Unconditioned and conditioned anxiolytic effects of Sodium Valproate on flavor neophobia and fear conditioning

In three experiments with rats, we analyzed the potential anxiolytic effects of sodium valproate, an anticonvulsant drug that has shown additional pharmacodynamic effects in animal models, including anxiolytic action. Since previous results have revealed that injecting valproate before allowing animals to consume a novel flavor solution resulted in an attenuation of neophobia, we predicted a similar effect when the novel flavor is presented on a drug-free trial in the presence of a context previously associated with the drug. In line with this hypothesis, in our first experiment we observed a reduction in neophobia to a novel flavor for those animals tested in the presence of the context associated with Sodium Valproate. However, a control group that received the drug before being allowed access to the novel flavor showed a significant reduction in consumption. Experiment 2 revealed that the unconditioned effects of the drug include a deleterious effect on the animals’ locomotor activity that probably interferes with drinking behavior. Finally, in a third experiment, we directly tested the potential anxiolytic properties of sodium valproate by injecting the drug before implementing a fear conditioning procedure. These findings are explained in terms of the unconditioned anxiolytic action of the drug and the formation of an association between the context and the effects of the drug that evokes a conditioned response reminiscent of such anxiolytic effect.