Haloperidol-induced disruption of conditioned avoidance responding: Attenuation by prior training or by anticholinergic drugs

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Abstract

Rats injected daily with haloperidol (0.15 mg/kg) failed to acquire a one-way active avoidance response over a 9 day period (10 traisl/day). When these animals were subsequently tested without haloperidol, on the first drug-free day they performed as well as animals given saline throughout the training period and significantly better than naive saline-treated animals on the first day of training. The performance of rats were trained for two days before receiving haloperidol was only partly blocked by the drug, while animals trained for 9 days before drug administration were immune to the disruptive effects. Three anticholinergic (muscarinic) drugs, atropine (10 mg/kg), scopolamine (1 mg/kg) and benztropine (2 mg/kg) significantly reversed the effect of haloperidol on the acquisition of the avoidance response. These results are similar to those observed after bilateral destruction of the dipaminergic nigroneostriatal projection and support the view that this system is critically involved in the acquisition of learned instrumental responses. The nature of the avoidance deficit produced by these treatments is discussed with reference on the possibility that they selectively block the initiation of voluntary motor responses. According to this hypothesis, the failure of these treatments to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motoric sequences that cannot be initiated voluntarily in response to the conditioned stimulus.

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