Conditioned increase of locomotor activity induced by haloperidol

Abstract

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.

Fig 1. Mean percent activity on conditioning days as a function of conditioning, and haloperidol dose.

Percent activity was collapsed across each 60 min session. The animals had received either 0.5 mg/kg or 2.0 mg/kg of haloperidol before (P: Paired) or after (U: Unpaired) being introduced in the context-CS for 60 min.

Fig 2. Mean percent activity on the drug-free test day as a function of conditioning, and haloperidol dose.

(A) Percent activity is represented collapsed across 10-min periods, and (B) across the complete 60-min session. The animals had received either 0.5 mg/kg or 2.0 mg/kg of haloperidol during the four days of the conditioning stage before (P: Paired) or after (U: Unpaired) been exposed for 60 min to the context-CS. Test session was drug-free.

Fig 3. Mean percent activity on conditioning days as a function of conditioning.

Percent activity was collapsed across each 60 min session. The animals had received 0.5 mg/kg of haloperidol before (P: Paired) or after (U: Unpaired) being introduced in the context-CS for 60 min.

Fig 4. Mean percent activity on the drug-free test day as a function of conditioning, and haloperidol dose.

(A) Percent activity is represented collapsed across 10-min periods, and (B) across the complete 60-min session. The animals had received 0.5 mg/kg of haloperidol during the four days of the conditioning stage before (condition P: Paired) or after (condition U: Unpaired) been exposed for 60 min to the context-CS. Test session was drug-free.