Review
Behavioral Satiety Sequence (BSS) for the Diagnosis of Drug Action on Food Intake

https://doi.org/10.1016/S0091-3057(98)00032-XGet rights and content

Abstract

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.

Section snippets

Description of the Behavioral Satiety Sequence (BSS)

The most detailed behavioral account of drug action on appetite can be gained by using the Behavioral Satiety Sequence (2) (BSS). Bindra and Blond (5) and Bolles (14) first observed that grooming occurred after eating and before resting. The BSS is a clearly identifiable stochastic progression of behavioral trends over time (not a strict deterministic sequence). The progression of the BSS is from an initial phase of eating, through peaks of active and grooming behavior, to an eventual phase of

Methodological Aspects of the BSS

The equipment needed to study the BSS is standard to most behavioral pharmacology laboratories. The researcher’s basic needs are an observation arena, video cameras, video recorder, monitor, and a PC with a behavioral coding package. The procedural details of the Leeds studies can be found in Halford and Blundell 30, 36 and Halford et al,. (38). We have also published a detailed account of our BSS methodology in Current Protocols in Neuroscience (36). For this review we will concentrate on

Food intake

Food intake can either be measured by weighing the difference in the food bowl before and after the observation or it can be measured automatically during the observation. Various forms of automated feeding devices are available.

Eating parameters

Eating parameters describe the relationship between changes in the amount of food eaten and changes in the various structural elements of eating behavior. Continuous observation is required to identify those parameters. Mean local eating rates (LER) (g/min), mean intake

Interpreting the BSS

The BSS, compiled from a true experiment showing the orderly changes in eating, grooming, and resting is shown in Fig. 2.

Drugs and the BSS

Table 3 shows the pharmacological action and the action on the BSS of the drugs mentioned in this section. The BSS profiles of some of the drugs mentioned in this section are shown in FIG. 4., FIG. 5..

Blundell and McArthur (12) were the first to use the BSS to compare the behavioral effects of the catecholaminergic agent, amphetamine with the serotonergic agent, fenfluramine. In simple food-intake tests, both drugs produced equal and highly potent reductions in food intake, but their temporal

5-HT Receptor Subtypes and the BSS

Although it is established that pharmacological manipulation of 5-HT reduces food intake while preserving the BSS, which 5-HT receptors mediate these effects? The 5-HT receptors implicated in satiety are 5-HT1b and 5-HT2c [see (21) for review], although a relative lack of highly selective 5-HT agonists and antagonists makes the investigation of the precise role of 5-HT1b and 5-HT2c sites difficult. For example, agonists of the 5-HT2c receptor generally have affinity for other 5-HT2 receptors

Other Compounds That Preserve the BSS

The BSS is not only produced by increasing CNS 5-HT levels or directly activating hypothalamic 5-HT1b and 5-HT2c receptors. Activation of peripheral 5-HT receptors, possibly in the gut, suppressed food intake and preserved the BSS (24). This may be related to the role of peripheral 5-HT in gastric motility and stomach emptying. Other peripheral satiety factors such as CCK (see previous) bombesin and enterostatin have also been shown to preserve the BSS. The behavioral effects of the ob-gene

Future Directions

To continue this work, newer, more selective neurochemicals that act on target appetite systems and on-going research to further characterize feeding behavior are both required. There are many aspects of behavior that could be utilized by researchers to more accurately characterize satiety, nausea, sedation, hyperactivity, and changes in palatability. Such measure could include direct measurement of food bowl weight over the full observation period to reveal changes in eating rates (g/min)

Summary

The BSS, first identified in its modern form by Smith’s group at Cornell, is widely recognized as a behavioral representation of the physiological processes of satiety set in operation by food ingestion. The BSS has been used to confirm the role of the gut peptide CCK in satiety. The BSS has been used to identify drugs that enhance satiety. The investigation of macro- and microstructural analysis of feeding behavior permits identification of differing mechanisms of drugs action not apparent in

Acknowledgements

This article was submitted following the “Neuropsychopharmacology of Motivation” symposium given in honor of L. J. Herberg.

References (73)

  • J.E. Hartley et al.

    The effects of WAY-100135 and 8-hydroxy-2-(di-n-propylamino)tetralin on feeding behaviour in the rat

    Eur. J. Pharmacol.

    (1994)
  • G.A. Kennett et al.

    5-HT1B agonists induce anorexia at a post synaptic site

    Eur. J. Pharmacol.

    (1987)
  • B.H. King et al.

    MK-212 increases rat plasma ACTH concentration by activation of the 5-HT1C receptor subtype

    Neurosci. Lett.

    (1989)
  • L.R. Kushner et al.

    Behavioural correlates of oral and psotingestive satiety in the rats

    Physiol. Behav.

    (1984)
  • C. Oberlander et al.

    Distinct functions for dopamine and serotonin in locomotor behaviourEvidence using the 5-HT1 agonist RU 24969 in globus pallidus-lesioned rats

    Neurosci. Lett.

    (1986)
  • H. Pöysä

    Measuring time budgets with instananeous samplingA cautionary note

    Anim. Behav.

    (1991)
  • I.N. Rusk et al.

    Microstructural analysis of the anorectic effect of N-0437, a highly selective dopamine D-2 agonist

    Brain Res.

    (1989)
  • K.J. Simansky et al.

    Behavioural mechanisms for the anorectic actions of the serotonin (5-HT) uptake inhibitor sertraline in ratsComparison with directly acting agonists

    Brain Res. Bull.

    (1990)
  • A.J. Strohmayer

    Abnormal feeding and postprandial behavioural responses to food deprivation in genetically obese mice

    Physiol. Behav.

    (1979)
  • J.H. Strubbe et al.

    Interaction between circadian and caloric control of feeding behaviour in the rat

    Physiol. Behav.

    (1986)
  • J.H. Strubbe et al.

    Effect of skeleton photoperiod and food availability on the cicardian pattern of feeding and drinking in rats

    Physiol. Behav.

    (1986)
  • D. Verge et al.

    Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype

    Eur. J. Pharmacol.

    (1985)
  • D.T. Wong et al.

    Suppression of food intake in rats by fluoxetineComparison of enatiomers and effects of serotonin antagonists

    Pharmacol. Biochem. Behav.

    (1988)
  • J. Altmann

    Observational study of behavior

    Behavior

    (1974)
  • J. Antin et al.

    Cholecystokinin elicits the complete behavioural sequence of satiety in rats

    J. Comput. Physiol. Psychol.

    (1975)
  • Arrington, S. A.: Time sampling studies of child behaviour. Psychol. Monogr. 51;...
  • D. Ary

    Mathematical prediction of sampling component of behaviour observation measurement error

    Behav. Assess.

    (1984)
  • D. Bindra et al.

    A time sample method for measuring general activity and its components

    Can. J. Psychol.

    (1958)
  • Blundell, J. E.; Latham, C. J.; Behavioural pharmacology of feeding. In: Silverstone, T., ed. Drugs and appetite....
  • J.E. Blundell

    Is there a role for 5-HT (5-Hydroxytryptamine) in feedling?

    Int. J. Obesity

    (1977)
  • Blundell, J. E.; Alikhan, H.: Analysing the structure and sequence of feeding in animals and man. In: Microcomputers,...
  • J.E. Blundell et al.

    Pharmacological manipulations of feeding behaviourPossible influences of serotonin and dopamine on food intake

  • Blundell, J. E.; McArthur, R. A.: Behavioural flux and feeding: Continuous monitoring of food intake and food...
  • J.E. Blundell et al.

    Behavioural structure and mechanisms of anorexiaCalibration of normal and abnormal inhibition of eating

    Brain Res. Bull.

    (1985)
  • R.C. Bolles

    Grooming behaviour in the rat

    J. Comput. Physiol. Psychol.

    (1960)
  • P.G. Clifton

    The neuropharmacology of meal patterning

  • Cited by (208)

    • Feeding

      2021, Encyclopedia of Behavioral Neuroscience: Second Edition
    View all citing articles on Scopus
    View full text