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Behavioural profile of exendin-4/naltrexone dose combinations in male rats during tests of palatable food consumption

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Abstract

Rationale

The glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 potently suppresses food intake in animals and humans. However, little is known about the behavioural specificity of this effect either when administered alone or when co-administered with another anorectic agent.

Objectives

The present study characterises the effects of exendin-4, both alone and in combination with naltrexone, on behaviours displayed by male rats during tests with palatable mash.

Methods

Experiment 1 examined the dose-response effects of exendin-4 (0.025–2.5 μg/kg, IP), while experiment 2 profiled the effects of low-dose combinations of the peptide (0.025 and 0.25 μg/kg) and naltrexone (0.1 mg/kg).

Results

In experiment 1, exendin-4 dose dependently suppressed food intake as well as the frequency and rate of eating. However, these effects were accompanied by dose-dependent reductions in all active behaviours and, at 2.5 μg/kg, a large increase in resting and disruption of the behavioural satiety sequence (BSS). In experiment 2, while exendin-4 (0.25 μg/kg) and naltrexone each produced a significant reduction in intake and feeding behaviour (plus an acceleration in the BSS), co-treatment failed to produce stronger effects than those seen in response to either compound alone.

Conclusion

Similarities between the behavioural signature of exendin-4 and that previously reported for the emetic agent lithium chloride would suggest that exendin-4 anorexia is related to the aversive effects of the peptide. Furthermore, as low-dose combinations of the peptide with naltrexone failed to produce an additive/synergistic anorectic effect, this particular co-treatment strategy would not appear to have therapeutic significance.

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  1. Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK, England

    F. L. Wright & R. J. Rodgers

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  1. F. L. Wright
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Correspondence to R. J. Rodgers.

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A preliminary report of experiment 1 was presented in the 15th Biennial Meeting of the European Behavioural Pharmacology Society in La Rochelle, France (September 6–9, 2013).

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Wright, F.L., Rodgers, R.J. Behavioural profile of exendin-4/naltrexone dose combinations in male rats during tests of palatable food consumption. Psychopharmacology 231, 3729–3744 (2014). https://doi.org/10.1007/s00213-014-3507-4

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