Abstract
The opiate antagonist naloxone can completely or partially reverse the effects of the benzodiazepines on appetitive behaviours and conflict tasks involving electric shook. If naloxone changes the anxiolytic action of the benzodiazepines it should, theoretically, be effective in tasks employing nonreward as well as those employing shock.
We tested naloxone and chlordiazepoxide on acquisition and performance of a nonreward task, DRL. With both continuous administration during acquisition of DRL, and intermittent administration during stable performance, chlordiazepoxide (5 mg/kg IP) increased burst responding and shifted the peak of the inter-response time (IRT) distribution curve to shorter IRTs. Naloxone (3 mg/kg IP) blocked the effects of chlordiazepoxide on acquisition of DRL. Naloxone (3 mg/kg and 10 mg/kg IP) did not change the effects of chlordiazepoxide on well-learned performance of the DRL schedule.
These results show that endogenous opiates could mediate some but not all of the actions of the benzodiazepines. They also suggest that state-dependent and “truly anxiolytic” effects of the benzodiazepines (McNaughton 1985) may have different pharmacological substrates.
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References
Billingsley ML, Kubena RK (1978) The effects of naloxone and picrotoxin on the sedative and anticonflict effects of bezodiazepines. Life Sci 22:897–906
Birk JC, Noble RG (1981) Naloxone antagonism of diazepam-induced feeding in the syrian Hamster. Life Sci 29:1125–1131
Britton DR, Britton KT, Dalton D, Vale W (1981) Effects of naloxone on anti-conflict and hyperphagic actions of diazepam. Life Sci 29:1297–1302
Cook L, Davidson AB (1973) Effects of behaviourally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven, New York, pp 327–345
Cooper SJ (1980) Naloxone: Effects on food and water consumption in the non-deprived and deprived rat. Psychopharmacology 71:1–6
Cooper SJ (1982) Effects of opiate antagonists and of morphine on CDP-induced hyperdipsia in the water deprived rat. Neuropharmacology 21:1013–1017
Cooper SJ (1983) Benzodiazepine-opiate antagonists in relation to anxiety and appetite. TIPS 456–458
Cooper SJ, Estall LB (1985) Behavioural pharmacology of food, water and salt intake in relation to drug actions at benzodiazepine receptors. Neurosci Biobehav Rev 9:5–20
Costa E, Guidotti A, Mao CC (1975) Evidence for the involvement of GABA in the action of benzodiazepines: studies of the rat cerebellum. In: Costa E, Greengard P (eds) Mechanism of action of benzodiazepines. Raven, New York, pp 113–120
Duka T, Cumin R, Haefely W, Herz A (1981) Naloxone blocks the effect of diazepam and meprobamate on conflict behaviour in rats. Pharmacol Biochem Behav 15:115–117
Duka T, Millan MJ, Ulsamer B, Doenicke A (1982) Naloxone attenuates the anxiolytic action of diazepam in man. Life Sci 31:1833–1836
Duka T, Wuster M, Herz A (1980) Benzodiazepines modulate striatal enkephalin levels via a GABAergic mechanism. Life Sci 26:771–776
File SE (1982) Chlordiazepoxide-induced ataxia, muscle relaxation and sedation in the rat: Effects of muscimol, picrotoxin and naloxone. Pharmacol Biochem Behav 17:1165–1170
Gray JA (1975) Elements in a two-process theory of learning. Academic, London
Gray JA (1977) Drug effects on fear and frustration: Possible limbic site of action of minor tranquillizers. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, volume 8. Plenum, New York, pp 433–529
Gray JA (1982) The Neuropsychology of anxiety. Oxford University Press, New York
Haefely W (1980) GABA and the anticonvulsant action of the benzodiazepines and barbiturates. Brain Res Bull 5 (suppl 2):873–878
Haefely W, Kulsar A, Mohler H, Pieri L, Polc P, Schaffner R (1975) Possible involvement of GABA in the central actions of benzodiazepines. Adv Biochem Psychopharmacol 14:131–151
Koob GF, Strecker RE, Bloom FE (1980) Effects of naloxone on the anticonflict properties of alcohol and chlordiazepoxide. Subst Alcohol Actions Misuse 1:447–457
McMillan DE, Campbell RJ (1970) Effects ofd-amphetamine and chlordiazepoxide on spaced responding in pigeons. J Exp Anal Behav 14:177–184
McNaughton N (1985) Chlordiazepoxide and successive discrimination: Different effects on acquisition and performance. Pharmacol Biochem Behav 23:487–494
Paul SM, Skolnick P (1982) Comparative neuropharmacology of antianxiety drugs. Pharmacol Biochem Behav 17 (suppl 1):37–41
Richelle M, Xhenseval B, Fontaine D, Thone L (1962) Action of chlordiazepoxide andd-amphetamine on responding maintained by a DRL schedule of reinforcement. Int J Neuropharmacol 1:381–391
Sanger DJ (1980) The effects of caffeine on timing behaviour in rodents, comparisions with chlordiazepoxide. Psychopharmacology 68:305–309
Sanger DJ (1985) Minireview GABA and the behavioural effects of anxiolytic drugs. Life Sci 36:1503–1513
Sanger DJ, Blackman DE (1975) The effects of tranquillizing drugs on timing behaviour in rats. Psychopharmacologia 44:153–156
Sanger DJ, Key M, Blackman DE (1974) Differential effects of CDP andd-amphetamine on responding maintained, by a DRL schedule of reinforcement. Psychopharmacologia 38:159–171
Snedecor GW, Cochran WG (1967) Statistical Methods. Iowa State University Press, Iowa
Soubrie P, Jobert A, Thiebot MH (1980) Differential effects of naloxone against the diazepam-induced release of behaviour in rats in three aversive situations. Psychopharmacology 69:101–105
Stapleton JM, Lind MD, Merriman VJ, Reid LD (1979) Naloxone inhibits diazepam-induced feeding in rats. Life Sci 24:2421–2426
Ticku MK (1983) Benzodiazepine-GABA receptor-ionophore complex. Current concepts. Neuropharmacology 22:1459–1470
Tripp G, McNaughton N (1986) Naloxone fails to block the effects of chlordiazepoxide on acquisition and performance of successive discrimination. Psychopharmacology 91:119–121
Zar JH (1974) Biostatistical analysis. Prentice-Hall, New Jersey
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Tripp, G., McNaughton, N. & Oei, T.P.S. Naloxone blocks the effects of chlordiazepoxide on acquisition but not performance of differential reinforcement of low rates of response (DRL). Psychopharmacologia 91, 112–118 (1987). https://doi.org/10.1007/BF00690938
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DOI: https://doi.org/10.1007/BF00690938