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.
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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
Berridge KC, Pecina S (1995) Benzodiazepines, appetite, and taste palatability. Neurosci Biobehav Rev 19:121–131
Berridge KC, Treit D (1986) Chlordiazepoxide directly enhances positive ingestive reactions in the rat. Pharmacol Biochem Behav 24:217–221
Cole SO (1983) Combined effects of chlordiazepoxide treatment and food deprivation on concurrent measures of feeding and activity. Pharmacol Biochem Behav 18:369–372
Cooper SJ (2004) Endocannabinoids and food consumption: comparisons with benzodiazepine and opioid palatability-dependant appetite. Eur J Pharmacol 500:37–49
Cooper SJ (2005) Palatability dependant appetite and benzodiazepines: new directions from the pharmacology of GABA(A) receptor subtypes. Appetite 44:133–150
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
Cooper SJ, Yearbury RE (1988) Clonazepam selectively increases saccharin ingestion in two-choice test. Brain Res 456:173–176
Ettinger RH, Staddon JER (1982) Decreased feeding associated with acute hypoxia in rats. Physiol Behav 29:455–458
Ettinger RH, Staddon JER (1983) Operant regulation of feeding: a static analysis. Behav Neurosci 97:639–653
Ettinger RH, Thompson S, Staddon JER (1986) Cholecystokinin, diet palatability, and feeding regulation in rats. Physiol Behav 36:801–809
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
Gray RW, Cooper SJ (1995) Benzodiazepines and palatability: taste reactivity in normal ingestion. Physiol Behav 58:853–859
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
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
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
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
Johnson DN (1978) Effect of diazepam on food consumption in rats. Psychopharmacology 56:111–112
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
Kelly J, Grossman SP (1980) GABA and hypothalamic feeding systems. Brain Res Bull 5:237–244
Leander JD (1983) Effects of punishment-attenuating drugs on deprivation-induced drinking: implications for conflict procedures. Drug Dev Res 3:185–191
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
Meddis R (1975) A simple two-group test for matched scores with unequal cell frequencies. Br J Psychol 66:225–227
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
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
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
Page EB (1963) Ordered hypothesis for multiple treatments: a significance test for linear ranks. J Am Stat Assoc 58:216–230
Parker LA (1995) Chlordiazepoxide enhances the palatability of lithium-amphetamine, and saline-paired saccharin solution. Pharmacol Biochem Behav 50:345–349
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
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
Poschel BPH (1971) A simple and specific screen for benzodiazepine-like drugs. Psychopharmacology 19:193–198
Randall LO (1960) Pharmacology of methaminodiazepoxide. Dis Nerv Syst 21:7–10
Randall LO, Schallek W, Heise GA, Keith EF, Bagdon RE (1960) The psychosedative properties of methaminodiazepoxide. J Pharmacol Exp Ther 129:163–171
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
Shephard RA (1987) Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine actions. Life Sci 40:2429–2436
Shephard RA, Broadhurst PL (1982) Effects of diazepam and picrotoxin on hyperphagia in rats. Neuropharmacology 21:771–773
Shephard RA, Estall LB (1984) Anxiolytic actions of chlordiazepixidedetermine effects on hyponeophagia in rats. Psychopharmacology 82:343–347
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
Treit D, Berridge KC (1990) A comparison of benzodiazepine, serotonin, and dopamine agents in the taste-reactivity paradigm. Pharmacol Biochem Behav 37:451–456
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
Tye NC, Nicholas DJ, Morgan MJ (1975) Chlordiazepoxide and preference for free food in rats. Pharmacol Biochem Behav 3:1149–1151
Wise RA, Dawson V (1974) Diazepam-induced eating and lever-pressing for food in sated rats. J Comp Physiol Psychol 86:930–941
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
Acknowledgement
This research was supported in part by the Wellcome Trust 063938/GM/KM/RL.
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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
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DOI: https://doi.org/10.1007/s00213-006-0412-5