Behavioural analysis of feeding: Implications for the pharmacological manipulation of food intake in animals and man

doi:10.1016/0364-7722(80)90002-8

Progress in Neuro-Psychopharmacology

Volume 4, Issues 4–5, 1980, Pages 319-326

Progress in Neuro-Ps...

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Abstract

1.
1. Certain techniques have been described for the behavioural characterization of the effects of drugs on feeding. These techniques are designed to reveal the way in which feeding behaviour is organised by examining the micro- and macro- structure of eating activities.
2.
2. In rats, results have a) revealed a behavioural profile of amphetamine anorexia, b) permitted a differentiation between the ways in which differing groups of pharmacological agents adjust food intake by altering the elements of feeding behaviour and c) drawn attention to the way in which anorexic drugs may reduce food intake by intervening in a natural system which matches food intake to energy demands or by merely obstructing normal feeding responses.
3.
3. In human studies the techniques have been used for two purposes: First to distinguish between the inhibitory actions on food intake of different anorexic drugs, and second to illustrate how long-term drug administration (e.g. phenothiazine treatment in psychotic patients) may promote weight gain by adjusting the basic pattern of feeding.

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Pharmacological manipulation of feeding: possible influences of serotonin and dopamine on food intake

J.E. Blundell et al.

Pharmacology of Food and Water Intake

Cited by (19)

Selective serotonin 5-HT<inf>2C</inf> receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues
2011, Neuropharmacology
Citation Excerpt :
Studies over the last 20 years have identified cellular and behavioral mechanisms of these appetitive processes to include dopamine, glutamate, and their intracellular signaling webs in the limbic–corticostriatal–hypothalamic circuit (Kelley, 2004). Serotonin (5-HT) is additionally important in the control over the affective and motivational aspects of palatable food and drug reward, which has been described to occur at the level of satiety (Hewitt et al., 2002; Lyness et al., 1980; Blundell et al., 1980) as well as palatability or reinforcing efficacy (Wogar et al., 1991). In particular, there is a growing literature based upon genetic and pharmacological manipulations that the serotonin 5-HT2C receptor (5-HT2CR) signaling regulates such neurobehavioral processes which may underlie important chronic health maladies including obesity, eating disorders and drug addiction (Halford et al., 2010; Bubar and Cunningham, 2008; Steiger, 2004).
Serotonin (5-HT) controls affective and motivational aspects of palatable food and drug reward and the 5-HT_2C receptor (5-HT_2CR) has emerged as a key regulator in this regard. We have evaluated the efficacy of a selective 5-HT_2CR agonist, WAY 163909, in cocaine and sucrose self-administration and reinstatement assays employing parallel experimental designs in free-fed rats. WAY 163909 dose-dependently reduced the reinforcing efficacy of cocaine (ID₅₀ = 1.19 mg/kg) and sucrose (ID₅₀ = 0.7 mg/kg) as well as reinstatement (ID₅₀ = 0.5 mg/kg) elicited by exposure to cocaine-associated contextual cues, but not sucrose-associated contextual cues. The ID₅₀ of WAY 163909 predicted to decrease the reinforcing efficacy of cocaine or sucrose as well as reinstatement upon exposure to cocaine-associated cues was ∼5–12-fold lower than that predicted to suppress horizontal ambulation (ID₅₀ = 5.89 mg/kg) and ∼2–5-fold lower than that predicted to suppress vertical activity (ID₅₀ = 2.3 mg/kg). Thus, selective stimulation of the 5-HT_2CR decreases the reinforcing efficacy of cocaine and sucrose in freely-fed rats, but differentially alters the incentive-salience value of cocaine- vs. sucrose-associated cues at doses that do not impair locomotor activity. Future research is needed to tease apart the precise contribution of 5-HT_2CR neurocircuitry in reward and motivation and the learning and memory processes that carry the encoding for associations between environmental cues and consumption of rewarding stimuli. A more complete preclinical evaluation of these questions will ultimately allow educated proof-of-concept trials to test the efficacy of selective 5-HT_2CR agonists as adjunctive therapy in chronic health maladies including obesity, eating disorders and drug addiction.
This article is part of a Special Issue entitled ‘Serotonin’.
Metergoline antagonizes fluoxetine-induced suppression of food intake but not changes in the behavioural satiety sequence
1996, Pharmacology Biochemistry and Behavior
In this study continuous monitoring was used to yield a true behavioural record. This allows a bidimensional account of drug effects on every unit of behaviour. Behavioural dimensions of duration (dur) and frequency (frq) measures were utilized to monitor the effects of an ED₅₀ anorectic dose of fluoxetine (10 mg/kg IP) on the behavioural satiety sequence and the effect of a metergoline (1 mg/kg IP) challenge. Fluoxetine reduced food intake by 45% (p < 0.005). The local eating rate was also reduced (p < 0.001), demonstrating a marked slowing of eating behaviour. Eating behaviour was reduced (frq p < 0.005) as was grooming (frq p < 0.05) and activity. Resting was increased (dur p < 0.05) and temporally advanced. There was no gross disruption of behaviour and the profile was adjusted in a way consistent with the expression of satiety. Fluoxetine-induced changes were very similar to those produced by prefeeding. Metergoline antagonised fluoxetine's effect on intake and eating duration (dur p < 0.05). However, metergoline did not antagonise the effect of fluoxetine on the frequency of eating (frq p < 0.005), thus increasing the amount consumed per eating episode. Grooming (frq p < 0.005) and activity also remained reduced. At this dose fluoxetine-induced suppression of eating is serotonin dependent as it is reversed by metergoline. Fluoxetine-induced suppression of eating at this dose is consistent with the normal operation of satiety. Fluoxetine-induced slowing of behaviour appears to be mediated by a separate mechanism.
Food and Water Intake
1994, Handbook of Behavioral Neuroscience
This chapter describes the various aspects of food and water intake in experimental studies. Food intake by the laboratory animal meets the energy requirements for maintenance, growth, physical activity, heat production, and other physiological processes. Water intake compensates for the losses by evaporation and by excretion in urine and feces. Food and water intake show a marked daily variation, as they are strongly coupled to the circadian rhythm of waking–sleeping behavior. Numerous biochemical and physiological factors are in turn connected with food and water intake and their subsequent daily variation may affect the responsiveness of the animal to experimental stimuli. The availability of food and water thus contributes to the dramatype of the experimental animal. The chapter presents a short description that is given of the eating and drinking behavior of mice and rats, and of the effects of some maintenance conditions on this behavior. Being one of the most often used motivating test conditions, food restriction is also discussed among the factors modulating drug effects on eating behavior.
Experimental manipulations of eating: Advances in animal models for studying anorectic agents
1987, Pharmacology and Therapeutics
The material set out in this text has been designed to show the wide range of procedures which have the capacity to modify eating behavior—to produce hyper- or hypophagia, to alter the profile of eating patterns, or to adjust dietary preferences and selection. Accordingly, in investigating anoretic drugs it seems necessary to observe the effects of drug actions in a variety of experimental models. This strategy will provide a more complete description of the effect of a drug, will throw light on the mechanism of action, and will provide a more realistic base for predicting the effects of drugs in man.
Neuropharmacology of drugs affecting food intake
1987, Pharmacology and Therapeutics
The importance of the central monoamines NE, DA and 5-HT in ingestive behavior has inevitably resulted in considerable effort being expended in attempting to implicate these monoamines in the mechanism of action of anorectic drugs. The statements that amphetamine-induced anorexia is unlikely to be due to central serotoninergic systems and that central noradrenergic and dopaminergic systems are not implicated in the appetite suppressant effect of fenfluramine are in all probalility correct. However, to attribute the ability of drugs to decrease food intake unequivocally to a specific effect on central monoaminergic systems is almost certainly an oversimplification, due to the fact that other putative neurotransmitters, such as GABA and peptides, play a critical role in eating. This can be achieved either directly or by modulating the release of other transmitters. An added complication in attempting to correlate a specific ceurochemical process to a behavioral effect, such as anorexia, is the complexity of the central actions of the drug. At best, a predominant but not an exclusive process can be identified. Perhaps the in-built constraint of attempting to correlate a specific neurochemical effect to the desired action of a drug is accountable for the absence of a second generation of centrally acting anorectic drugs.
Dramatic progress has been made in elucidating the factors involved in ingestive behavior over the last 5–10 years. This information should, and must, provide the catalyst for more efficacious anorectic drugs because obesity represents one of the few major diseases for which adequate drug therapy does not exist.
Hypothalamic serotonin in the control of meal patterns and macronutrient selection
1986, Brain Research Bulletin
Serotonin (5-HT) is believed to have an inhibitory influence over feeding behavior. The present experiments were designed to investigate the effects of hypothalamic 5-HT on spontaneously motivated feeding and appetite regulation. Freely-feeding rats were injected with 5-HT or norfenfluramine (NORFENF) directly into the paraventricular hypothalamus (PVN), and precise changes in feeding behavior were monitored by a computer. Following PVN 5-HT or NORFENF injection, animals exhibited a marked suppression in food intake, associated with a decrease in meal size, duration and eating rate and no change in the frequency of meals consumed. This suggests that brain 5-HT may influence primarily the induction of satiety rather than the suppression of hunger. The effect of drugs presumed to affect brain 5-HT transmission on diet selection was also investigated in groups of rats injected centrally with 5-HT or NORFENF or peripherally with either fenfluramine, quipazine or cyproheptadine. In a series of 2-diet tests, rats centrally injected with 5-HT or NORFENF exhibited a selective suppression of the carbohydrate-rich diets. In animals provided with three pure macronutrient diets, protein, carbohydrate and fat, systemic administration of serotonergic agents had its greatest impact on fat and carbohydrate ingestion, as compared to protein consumption. These findings support a role for hypothalamic 5-HT in modulating meal patterns and appetite for particular macronutrients.

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Special topic: Mechanisms of anorexia induced by drugsBehavioural analysis of feeding: Implications for the pharmacological manipulation of food intake in animals and man

Abstract

Psychosom

Physiol. Behav.

J. Psychiat. Res.

Eur. J. Pharmacol.

Life Sci.

Combined reserpine-chlorpromazine in the treatment of disturbed psychotics

Arch. Neurol. Psychiat.

Strategies and tactics in the use of anti-obesity drugs

Lancet

Is there a role for serotonin (5-hydroxytryptamine) in feeding?

Int. J. Obesity

Serotonin and Feeding

Pharmacological manipulation of feeding: possible influences of serotonin and dopamine on food intake

Pharmacology of Food and Water Intake

Special topic: Mechanisms of anorexia induced by drugs
Behavioural analysis of feeding: Implications for the pharmacological manipulation of food intake in animals and man