Methods for Determining the Specificity of Drug Effects on Feeding

Research into the effects of drugs on feeding has been guided by an interest in the neurochemical mechanisms involved in the control of food intake and by a desire to find safe, effective pharmacological treatments for feeding disorders such as obesity. Many experiments in the field have revealed that a multitude of compounds with widely different pharmacological actions can alter the food intake of laboratory animals. Although this undoubtedly reflects the complexity of the neurochemical control of feeding, it is likely that many of these drug effects result from general disturbances in behavior rather than from an action upon the neural systems involved in feeding. Often in such experiments the only data collected are the amounts of food consumed over brief time periods following acute drug treatment. This information is obviously important, but it is insufficient to allow any conclusions to be drawn about the specificity of action of the drug on feeding behavior. In the case of a drug-induced decrease in feeding, many possible explanations can be advanced to account for this result. Table 1 illustrates several such explanations, which can be divided into two categories: those concerned with nonspecific disruptions of behavior and those concerned with direct actions on feeding behavior. The task of the researcher interested in the effects of drugs on feeding is to decide between such alternative explanations. In many cases observation of drug-treated animals will reveal whether feeding is being disrupted by the occurrence of abnormal or stereotyped behaviors or by gross changes in locomotor activity. However, observational analysis alone will not in general permit a distinction to be made between, for example, drug-induced changes in the initiation, maintenance, or termination of feeding bouts and a change in the requirement for a particular macronutrient.

Nonspecific Actions

Response competition from other normal behaviors, e.g., drinking, sleeping, and motor activity, that displace feeding

Inability to perform the motor responses required for eating

Disruption of the sequencing of behavior leading to the initiation of feeding

Response competition from abnormal behavior, e.g., amphetamineinduced stereotypy

Drug-induced malaise

Deflection of attention to nonsalient aspects of the environment

Specific actions

Decreased requirement for calorles

Alteration m the initiation, maintenance or termination of feeding bouts (perhaps reflecting changes in hunger, appetite, or satiety)

Change in the circadian rhythm underlying feeding

Decreased requirement for a particular nutrient, e.g., protein, carbohydrate, or fat

Shift in preference for the sensory properties of foods, e.g., taste and texture, or reduction in incentive value of food

a Based on Blundell and Latham (1982)