Skip to main content
Log in

An operant determination of the behavioral mechanism of benzodiazepine enhancement of food intake

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

A recent review paper by Cooper (Appetite 44:133–150, 2005) has pointed out that a role for benzodiazepines as appetite stimulants has been largely overlooked. Cooper’s review cited several studies that suggested the putative mechanism of enhancement of food intake after benzodiazepine administration might involve increasing the perceived pleasantness of food (palatability).

Objectives

The present study examined the behavioral mechanism of increased food intake after benzodiazepine administration.

Materials and methods

The cyclic-ratio operant schedule has been proposed as a useful behavioral assay for differentiating palatability from regulatory effects on food intake (Ettinger and Staddon, Physiol Behav 29:455–458, 1982 and Behav Neurosci 97:639–653, 1983). The current study employed the cyclic-ratio schedule to determine whether the effects on food intake of chlordiazepoxide (CDP) (5.0 mg/kg), sodium pentobarbital (5.0 mg/kg), and picrotoxin (1.0 mg/kg) were mediated through palatability or regulatory processes.

Results

The results of this study show that both the benzodiazepine CDP and the barbiturate sodium pentobarbital increased food intake in a manner similar to increasing the palatability of the ingestant, and picrotoxin decreased food intake in a manner similar to decreasing the palatability of the ingestant.

Conclusions

These results suggest that the food intake enhancement properties of benzodiazepines are mediated through a mechanism affecting perceived palatability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Anderson-Baker WC, McLaughlin CL, Baile CA (1979) Oral and hypothalamic injections of barbiturates, benzodiazepines and cannabinoids and food intake in rats. Pharmacol Biochem Behav 11:487–491

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Pecina S (1995) Benzodiazepines, appetite, and taste palatability. Neurosci Biobehav Rev 19:121–131

    Article  PubMed  CAS  Google Scholar 

  • Berridge KC, Treit D (1986) Chlordiazepoxide directly enhances positive ingestive reactions in the rat. Pharmacol Biochem Behav 24:217–221

    Article  PubMed  CAS  Google Scholar 

  • Cole SO (1983) Combined effects of chlordiazepoxide treatment and food deprivation on concurrent measures of feeding and activity. Pharmacol Biochem Behav 18:369–372

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ (2004) Endocannabinoids and food consumption: comparisons with benzodiazepine and opioid palatability-dependant appetite. Eur J Pharmacol 500:37–49

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ (2005) Palatability dependant appetite and benzodiazepines: new directions from the pharmacology of GABA(A) receptor subtypes. Appetite 44:133–150

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ, Estall LB (1985) Behavioral pharmacology of food, water and salt intake in relation to drug actions at benzodiazepine receptors. Neurosci Biobehav Rev 9:5–19

    Article  PubMed  CAS  Google Scholar 

  • Cooper SJ, Yearbury RE (1988) Clonazepam selectively increases saccharin ingestion in two-choice test. Brain Res 456:173–176

    Article  PubMed  CAS  Google Scholar 

  • Ettinger RH, Staddon JER (1982) Decreased feeding associated with acute hypoxia in rats. Physiol Behav 29:455–458

    Article  PubMed  CAS  Google Scholar 

  • Ettinger RH, Staddon JER (1983) Operant regulation of feeding: a static analysis. Behav Neurosci 97:639–653

    Article  PubMed  CAS  Google Scholar 

  • Ettinger RH, Thompson S, Staddon JER (1986) Cholecystokinin, diet palatability, and feeding regulation in rats. Physiol Behav 36:801–809

    Article  PubMed  CAS  Google Scholar 

  • Foltin RW, Ellis S, Schuster CR (1985) Specific antagonism by Ro 15-1788 of benzodiazepine-induced increases in food intake in rhesus monkeys. Pharmacol Biochem Behav 23:249–253

    Article  PubMed  CAS  Google Scholar 

  • Gray RW, Cooper SJ (1995) Benzodiazepines and palatability: taste reactivity in normal ingestion. Physiol Behav 58:853–859

    Article  PubMed  CAS  Google Scholar 

  • Grill HJ, Norgren R (1978) The taste-reactivity test: I. Mimetic response to gustatory stimuli in neurologically normal rats. Brain Res Bull 143:263–279

    CAS  Google Scholar 

  • Higgs S, Cooper SJ (1995) Benzodiazepine receptor inverse agonists and ingestive behavior: the palatability hypothesis. In: Sarter M, Nutt DJ, Lister RG (eds) Benzodiazepine receptor inverse agonists. Wiley-Liss, New York, pp 163–184

    Google Scholar 

  • Higgs S, Cooper SJ (1996) Effects of the benzodiazepine receptor agonist Ro15-4513 on the ingestion of sucrose and sodium saccharin solutions: a microstructural analysis of licking behavior. Behav Neurosci 110:559–566

    Article  PubMed  CAS  Google Scholar 

  • Higgs S, Cooper SJ (2000) The effect of the dopamine D2 receptor antagonist raclopride on the pattern of licking microstructure induced by midazolam in the rat. Eur J Pharmacol 409:73–80

    Article  PubMed  CAS  Google Scholar 

  • Johnson DN (1978) Effect of diazepam on food consumption in rats. Psychopharmacology 56:111–112

    Article  PubMed  CAS  Google Scholar 

  • Kelly J, Grossman SP (1979) GABA and hypothalamic feeding systems. II. A comparison of GABA, glycine and acetylcholine agonists and their antagonists. Pharmacol Biochem Behav 11:647–652

    Article  PubMed  CAS  Google Scholar 

  • Kelly J, Grossman SP (1980) GABA and hypothalamic feeding systems. Brain Res Bull 5:237–244

    Article  CAS  Google Scholar 

  • Leander JD (1983) Effects of punishment-attenuating drugs on deprivation-induced drinking: implications for conflict procedures. Drug Dev Res 3:185–191

    Article  CAS  Google Scholar 

  • Martin JR, Schock P, Jenck F, Moreau JL, Haefely WE (1993) Pharmacological characterization of benzodiazepine receptor ligands with intrinsic efficacies ranging from high to zero. Psychopharmacology 111:415–422

    Article  PubMed  CAS  Google Scholar 

  • Meddis R (1975) A simple two-group test for matched scores with unequal cell frequencies. Br J Psychol 66:225–227

    Google Scholar 

  • Naruse T, Asami T, Koizumi Y (1988) Effects of naloxone and picrotoxin on diazepam- or pentobarbital-induced hyperphagia in nondeprived rats. Pharmacol Biochem Behav 31:709–711

    Article  PubMed  CAS  Google Scholar 

  • O’Hare E, Tierney KJ, Shephard RA (1991) Cyclic-ratio schedule analysis of a serotonin agonist and depletor on consummatory behaviour. Physiol Behav 29:331–334

    Article  Google Scholar 

  • O’Hare E, Levine AS, Semotuk MT, Tierney KJ, Shephard RA, Grace MK, Cleary J (1996) Utilization of a novel model of food reinforced behavior involving neuropeptide-Y, insulin, 2-deoxy-d-glucose and naloxone. Behav Pharmacol 7:742–753

    PubMed  Google Scholar 

  • Page EB (1963) Ordered hypothesis for multiple treatments: a significance test for linear ranks. J Am Stat Assoc 58:216–230

    Article  Google Scholar 

  • Parker LA (1995) Chlordiazepoxide enhances the palatability of lithium-amphetamine, and saline-paired saccharin solution. Pharmacol Biochem Behav 50:345–349

    Article  PubMed  CAS  Google Scholar 

  • Paul V, Ekambaram P (2005) Effects of sodium nitroprusside, a nitric oxide donor, on gamma-aminobutyric acis concentration in the brain and on picrotoxin-induced convulsions in combination with phenobarbitone in rats. Pharmacol Biochem Behav 80:363–370

    Article  PubMed  CAS  Google Scholar 

  • Posadas-Andrews A, Burton MJ, Cooper SJ (1985) Chlordiazepoxide and food-depravation compared using a food-preference test in the rat. Rev Mex Anal Conducta 11:21–30

    Google Scholar 

  • Poschel BPH (1971) A simple and specific screen for benzodiazepine-like drugs. Psychopharmacology 19:193–198

    Article  CAS  Google Scholar 

  • Randall LO (1960) Pharmacology of methaminodiazepoxide. Dis Nerv Syst 21:7–10

    PubMed  Google Scholar 

  • Randall LO, Schallek W, Heise GA, Keith EF, Bagdon RE (1960) The psychosedative properties of methaminodiazepoxide. J Pharmacol Exp Ther 129:163–171

    PubMed  CAS  Google Scholar 

  • Seoane JR, Baile CA (1973) Feeding behaviour in sheep as related to the hypnotic activities of barbiturates injected into the third ventricle. Pharmacol Biochem Behav 1:47–53

    Article  PubMed  CAS  Google Scholar 

  • Shephard RA (1987) Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine actions. Life Sci 40:2429–2436

    Article  PubMed  CAS  Google Scholar 

  • Shephard RA, Broadhurst PL (1982) Effects of diazepam and picrotoxin on hyperphagia in rats. Neuropharmacology 21:771–773

    Article  PubMed  CAS  Google Scholar 

  • Shephard RA, Estall LB (1984) Anxiolytic actions of chlordiazepixidedetermine effects on hyponeophagia in rats. Psychopharmacology 82:343–347

    Article  PubMed  CAS  Google Scholar 

  • Shephard RA, Hamilton MS (1989) Chlordiazepoxide and valproate enhancement of saline drinking by nondeprived rats: effects of bicuculline, picrotoxin and Ro 15-1788. Pharmacol Biochem Behav 33:285–290

    Article  PubMed  CAS  Google Scholar 

  • Treit D, Berridge KC (1990) A comparison of benzodiazepine, serotonin, and dopamine agents in the taste-reactivity paradigm. Pharmacol Biochem Behav 37:451–456

    Article  PubMed  CAS  Google Scholar 

  • Treit D, Berridge KC, Schultz CE (1987) The direct enhancement of positive palatability by chlordiazepoxide is antagonized by Ro15-1788 and CGS 8216. Pharmacol Biochem Behav 26:709–714

    Article  PubMed  CAS  Google Scholar 

  • Tye NC, Nicholas DJ, Morgan MJ (1975) Chlordiazepoxide and preference for free food in rats. Pharmacol Biochem Behav 3:1149–1151

    Article  PubMed  CAS  Google Scholar 

  • Wise RA, Dawson V (1974) Diazepam-induced eating and lever-pressing for food in sated rats. J Comp Physiol Psychol 86:930–941

    Article  PubMed  CAS  Google Scholar 

  • Yerbury RE, Cooper SJ (1987) The benzodiazepine partial agonist, Ro16-6028 and Ro17-1812, increase palatable food consumption in nondeprived rats. Pharmacol Biochem Behav 28:427–431

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This research was supported in part by the Wellcome Trust 063938/GM/KM/RL.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to E. O’Hare.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Hare, E., Kim, EM. & Tierney, K.J. An operant determination of the behavioral mechanism of benzodiazepine enhancement of food intake. Psychopharmacology 187, 138–142 (2006). https://doi.org/10.1007/s00213-006-0412-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0412-5

Keywords

Navigation