Abstract
Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3–5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0–9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.
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Barrett JE, Brady LS, Witkin JM (1985) Behavioral studies with anxiolytic drugs. I. Interaction of the benzodiazepine antagonist RO 15-1788 with chlordiazepoxide, pentobarbital and ethanol. J Pharmacol Exp Ther 226:554–559
Braestrup C, Schmiechen R, Neef G, Nielsen M, Petersen EN (1982) Interaction of convulsive ligands with benzodiazepine receptors. Science 216:1241–1243
Braestrup C, Nielsen M, Honore T, Jensen LH, Petersen EN (1983) Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 22:1451–1457
Cooper SJ (1980) Benzodiazepines as appetite-enhancing compounds. Appetite 1:7–19
Cooper SJ (1982a) Benzodiazepine mechanisms and drinking in the water-deprived rat. Neuropharmacology 21:775–780
Cooper SJ (1982b) Enhancement of osmotic- and hypovolemic-induced drinking by chlordiazepoxide in rats is blocked by naltrexone. Pharmacol Biochem Behav 17:921–925
Cooper SJ (1983) Benzodiazepines, barbiturates and drinking. In: Cooper SJ (ed) Theory in psychopharmacology. vol 2. Academic Press, London, pp 115–148
Cooper SJ (1985) A microgram dose of diazepam produces specific inhibition of ambulation in the rat. Pharmacol Biochem Behav 22:25–30
Cooper SJ (1986) Effects of the Beta-carboline FG 7142 on saccharin preference and quinine aversion in water-deprived rats. Neuropharmacology 25:213–216
Cooper SJ, Francis RL (1979) Water intake and time course of drinking after single or repeated chlordiazepoxide injections. Psychopharmacology 65:191–195
Cooper SJ, Moores WR (1985) Chlordiazepoxide-induced hyperphagia in non-food deprived rats: effects of RO 15-1788, CGS 8216 and ZK 93 426. Eur J Pharmacol 112:39–45
Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E (1983) β-carbolines enhance shock-induced suppression of drinking in rats. Proc Natl Acad Sci USA 80:2072–2076
Dantzer R, Perio A (1982) Behavioural evidence for partial agonist properties of RO 15-1788, a benzodiazepine receptor antagonist. Eur J Pharmacol 81:655–658
Falk JL (1969) The motivational properties of schedule induced polydipsia. J Exp Anal Behav 9:19–25
Falk JL (1971) The nature and determinants of adjunctive behavior. Physiol Behav 6:577–588
File SE, Pellow S (1986) Intrinsic actions of the benzodiazepine receptor antagonist RO 15-1788, Psychopharmacology 88:1–11
Hunkeler W, Mohler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516
Karobath M, Supavilai P, Borea PA (1983) Distinction of benzodiazepine receptor agonists and inverse agonists by binding studiesin vitro. In: Biggio G and Costa E (eds) Benzodiazepine recognition site ligands: biochemistry and pharmacology. New York, Raven Press, pp 129–137
Maickel RP, Maloney GJ (1973) Effects of various depressant drugs on deprivation-induced water consumption. Neuropharmacology 12:777–782
Maickel RP, Maloney GJ (1974) Taste phenomena influences on stimulation of deprivation-induced fluid consumption of rats. Neuropharmacology 13:763–767
McKearney JW (1973) Effects of methamphetamine and chlordiazepoxide on schedule controlled and adjunctive licking in the rat. Psychopharmacologia 30:375–384
Mohler H, Burkard WP, Keller HH, Richards JG, Haefely W (1981) Benzodiazepine antagonist RO 15-1788: Binding characteristics and interaction with drug-induced changes in dopamine turnover and cerebellar cCMP levels. J Neurochem 27:714–722
Pellow S, File SE (1984) Multiple sites of action for anxiogenic drugs: Behavioral, electrophysiological and biochemical correlations. Psychopharmacology 83:304–315
Polc P, Laurent JP, Scherschlicht R, Haefely W (1981) Electrophysiological studies on the specific benzodiazepine antagonist RO 15-1788. Naunyn Schmiedebergs Arch Pharmacol 316:317–325
Riley AL, Lovely RH (1978) Chlordiazepoxide-induced reversal of an amphetamine-established aversion: dipsogenic effects. Physiol Psychol 6:488–492
Robbins TW, Roberts DCS, Koob GF (1983) Effects ofd-amphetamine and apomorphine upon operant behavior and schedule-induced licking in rats with 6-hydroxydopamine-induced lesions of the nucleus accumbens. J Pharmacol Exp Ther 224:662–673
Roper TJ (1978) Diversity and substitutability of adjunctive activities under fixed-interval schedules of food reinforcement. J Exp Anal Behav 30:83–96
Sanger DJ, Blackman DE (1975) The effects of chlordiazepoxide on the development of adjunctive drinking in rats. Q J Exp Psychol 27:499–505
Sanger DJ, Blackman DE (1976) Effects of diazepam and ripazepam on two measures of adjunctive drinking in rats. Pharmacol Biochem Behav 5:139–142
Smith JB, Clark FC (1975) Effects ofd-amphetamine, chlorpromazine and chlordiazepoxide on intercurrent behavior during spaced responding schedules. J Exp Anal Behav 24:241–248
Soubrie P, DeAngelis L, Simon P, Boissier JR (1976) Effects des anxiolytiques sur la prise de boisson en situation nouvelle et familiere. Psychopharmacology 50:41–45
Squires RF, Braestrup C (1977) Benzodiazepine receptors in rat brain. Nature 266:732–734
Stephens DN, Shearman GT, Kehr W (1984) Discriminative stimulus properties of β-carbolines characterized as agonists and inverse agonists at central benzodiazepine receptors. Psychopharmacology 83:233–239
Trulson ME (1984) Effects of diazepam on behavior and dopamine-containing substantia nigra units in freely moving cats. Psychopharmacology 84:91–95
Turkish S, Cooper SJ (1984) Enhancement of saline consumption by chlordiazepoxide in thirsty rats: Antagonism by Ro 15-1788. Pharmacol Biochem Behav 20:869–873
Wetherington CL (1982) Is adjunctive behavior a third class of behavior? Neurosci Biobehav Rev 6:329–350
Williams JL, White JM (1984) The effects of amphetamine and scopolamine on adjunctive drinking and wheel-running in rats. Psychopharmacology 82:360–367
Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New York
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Mittleman, G., Jones, G.H. & Robbins, T.W. Effects of diazepam, FG 7142, and RO 15-1788 on schedule-induced polydipsia and the temporal control of behavior. Psychopharmacology 94, 103–109 (1988). https://doi.org/10.1007/BF00735889
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DOI: https://doi.org/10.1007/BF00735889