Behavioral satiety sequence (BSS) for the diagnosis of drug action on food intake.

The Behavioral Satiety Sequence (BSS) is the name given to the orderly transitions of eating, activity grooming and resting measured during the postingestive period. Because the BSS is considered to reflect the operations of natural physiological processes underlying satiety, the sequence can be used to discriminate between different drugs (and other manipulations) that reduce food intake via these natural physiological mechanisms or those that do so by interference. The BSS is only produced by the presence of a caloric load in the gut, and the preabsorptive satiety factors (such as CCK) the caloric load triggers. The BSS is most accurately defined by continuous observation rather than time or event sampling techniques [Partial Time Sampling (PTS) or Momentary Time Sampling (MTS)]. Continuous observation also allows the true duration and true frequency of each behavior to be analyzed. Continuous observation can be used to determine if the profiles associated with the reduction in food intake is caused by nausea, sedation, hyperactivity, or altered palatability of food. At the present time is it possible to identify a number of drugs whose suppression of food intake is associated with the disruption or preservation of the BSS. Drugs that increase synaptic 5-HT activity such d-fenfluramine, fluoxetine. and sibutramine all preserve the BSS and advance the onset of resting. The 5-HT1b/2c agonists mCPP and TFMPP and the 5-HT1b agonist CP-94,253 produce similar effects. However, the 5-HT2 agonist DOI and the 5-HT1a/1b agonist RU-24969 disrupt the BSS by inducing hyperactivity as does amphetamine. The 5-HT2 agonist MK-212 disrupts the BSS by inducing sedation. Selective dopamine agonists, at low doses, such as SKF-38393 (DA1) and LY-171555 (DA2) also preserve the BSS. However, detailed behavioral analysis of the effects of many recently discovered putative satiety factors remains to be carried out.