Conditioned avoidance responding

Fibiger HC, Zis AP, Phillips AG (1975) Haloperidol-induced disruption of conditioned avoidance responding attenuation by prior training or by anticholinergic drugs. Eur J Pharmacol 30 309-314. 

A simple butyrophenone, azabuperone (25), was found to produce catalepsy, give a positive response in conditioned avoidance responding, and block amphetamine stereotyped behavior in rats. The compound is currently being used clinically as an antipsychotic agent. 37... 

Pyrrole Mannich bases have been prepared as potential antipsychotic agents that do not have the extrapyramidal side effects (EPS). In one case, A -methylpyrrole was amidomethylated with l-(hydroxymethyl)azepan-2-one, which was assembled by condensation between the seven-membered lactam and formaldehyde. The amidomethylated 7V-methylpyrrole then underwent the Mannich reaction with arylpiperazine and formaldehyde in the presence of trifluoroacetic acid (TEA). The pyrrole Mannich bases synthesized in this manner exhibited a high affinity for the serotonin 5-HT-lA and 5-HT-lB binding sites. Although these arylpiperazines interact weakly with dopamine D-1 and D-2 receptors, they were reasonably potent in an in vivo model in the rat CAR (conditioned avoidance responding), an indication of potent antipsychotic activity. 

Perhaps the oldest animal model to predict potential antipsychotic drug efficacy is the conditioned avoidance response (CAR) (108, 112, 181, 182). In the conditioned reinforcement model, experimental animals are trained to perform a certain response to avoid a mild shock. Trained avoidance responses may be active (pressing a lever, climbing a pole, or jumping out of a box) or passive (remaining in the darker of two compartments). Classical antipsychotic drugs and benzodiazepines reduce avoidance responding at doses that do... 

Subjective-effect studies require consideration of several experimental factors and control procedures. Participants must be able to comprehend and respond appropriately to questionnaires. Drugs should be administered under double-blind conditions to avoid the introduction of bias into participants reports. The participants prior drug exposure could influence responding most studies assessing abuse potential have used participants with histories of illicit drug use, though a number of studies have been conducted in healthy volunteers without histories of drug abuse.40,44-47... 

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