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.

Temporal Factors Modulate Haloperidol-Induced Conditioned Catalepsy.

Repeated pairings of a neutral context and the effects of haloperidol give rise to conditioned catalepsy when the context is subsequently presented in a drug-free test. In order to confirm whether this response is based on Pavlovian processes, we conducted two experiments involving two manipulations that affect conditioning intensity in classical conditioning procedures: time of joint exposure to the conditioned and the unconditioned stimulus, and the length of the inter-stimulus interval (ISI). The results revealed that both an increase in the length of context-drug pairings during conditioning and a reduced ISI between drug administration and context exposure increased conditioned catalepsy. These results are discussed in terms of the temporal peculiarities of those procedures that involve drugs as the unconditioned stimulus along with the role of Pavlovian conditioning in context-dependent catalepsy.

Haloperidol-based conditioned increase in locomotor activity is disrupted by latent inhibition and extended interstimulus interval.

Previous research have shown that repeated administration of 0.5 mg/kg of haloperidol in a given context gives rise to an increase in activity when spontaneous locomotor activity is recorded in a drug-free test conducted in such context. In order to confirm whether this type of response is based on processes of a Pavlovian nature, we conducted two experiments involving two manipulations that disrupt conditioning in typical classical conditioning procedures: preexposure of the to-be-conditioned stimulus (latent inhibition), and an increase in the length of the inter-stimulus interval. The results revealed that both manipulations were effective in reducing the conditioned increase of the locomotor response. This kind of conditioning can be explained in terms of the differential effects of low vs. high doses of haloperidol, and the temporal dynamics of conditioned response.

Conditioned increase of locomotor activity induced by haloperidol.

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol can act as an unconditioned stimulus, we carried out two experiments in which the administration of haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase in locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.