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Behavioral Pharmacology of Antianxiety Drugs

  • Chapter
Handbook of Psychopharmacology

Abstract

The discovery and introduction of valuable new antianxiety agents into clinical psychotherapeutics within the last 20 years was accompanied by a parallel advance in the development of behavioral pharmacology. Behavioral methodology helped to characterize these new agents. At the same time, the interesting and varied properties of these compounds stimulated the development of more comprehensive behavioral techniques so that possible subtle differences among the compounds could be evaluated. In this chapter, we shall review behavioral studies in animals that may shed light upon the therapeutic actions of benzodiazepines and other antianxiety drugs. Although many pharmacologic techniques have been used to study the central nervous system actions of antianxiety agents, e.g., antagonism of pentylene-tetrazol-induced convulsions or footschock-induced fighting, most of the material to be reviewed will involve operant conditioning techniques. The advantages of operant methods, including the use of animals as their own controls because of the availability of stable baselines in trained animals, have been described previously (Cook and Sepinwall, 1975a,b). Some material will be included, however, to indicate the Value of certain nonoperant behavioral procedures for studying anxiolytic compounds.

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References

  • Aron, C., Simon, P., Larousse, C., and Boissier, J. R., 1971, Evaluation of a rapid technique for detecting minor tranquilizers, Neuropharmacology10:459–469.

    PubMed  Google Scholar 

  • Ashton, H„ Millman, J. E., Telford, R., and Thompson, J. W., 1976, A comparison of some physiological and psychological effects of propranolol and diazepam in normal subjects, Br. J. Clin. Pharmacol.3:551–559.

    PubMed  Google Scholar 

  • Babbini, M., Torrielli, M. V., Gaiardi, M., Bartoletti, M., and DeMarchi, F., 1974, Central effects of three fluorinated benzodiazepines in comparison with diazepam, Pharmacology12:74–83.

    PubMed  Google Scholar 

  • Babbini, M., Gaiardi, M., Bartoletti, M., Torrielli, M. V., and DeMarchi, F., 1975, The conflict behavior in rats for the evaluation of a homogeneous series of 3-hydroxybenzo-diazepines: Structure-activity relationships, Pharmacol. Res. Commun.7:337–346.

    Google Scholar 

  • Bainbridge, J. G., 1968, The effect of psychotropic drugs on food reinforced behaviour and on food consumption, Psychopharmacologia12:204–213.

    Google Scholar 

  • Barrett, J. E., 1976, Effects of alcohol, chlordiazepoxide, cocaine and pentobarbital on responding maintained under fixed-interval schedules of food or shock presentation, J. Pharmacol. Exp. Ther.196:605–615.

    Google Scholar 

  • Barrett, J. E., and Witkin, J. M., 1976, Interaction of d-amphetamine with pentobarbital and chlordiazepoxide: Effects on punished and unpunished behavior in pigeons, Pharmacol. Biochem. Behav.5:285–292.

    PubMed  Google Scholar 

  • Bassett, J. R., and Cairncross, K. D., 1974, Effects of psychoactive drugs on responses of the rat to aversive stimulation, Arch. Int. Pharmacodyn. Ther.212:221–229.

    PubMed  Google Scholar 

  • Beer, B., and Migler, B., 1975, Effects of diazepam on galvanic skin response and conflict in monkeys and humans, in: Predictability in Psychopharmacology (A. Sudilovsky, S. Gershon, and B. Beer, eds.), pp. 143–158, Raven Press, New York.

    Google Scholar 

  • Beer, B., Chasin, M., Clody, D. E., Vogel, J. R., and Horovitz, Z. P., 1972, Cyclic adenosine monophosphate phosphodiesterase in brain: Effect on anxiety, Science176:428–430.

    PubMed  Google Scholar 

  • BiGnami, G., 1976, Behavioral pharmacology and toxicology, Annu. Rev. Pharmacol.16:329–366.

    Google Scholar 

  • Blakely, T. A., and Parker, L. F., 1973, The effects of parachlorophenylalanine on experimentally induced conflict behavior, Pharmacol. Biochem. Behav.1:609–613.

    PubMed  Google Scholar 

  • Boissier, J.-R., and Simon, P., 1964, Dissociation de deux composantes dans le comportement d’investigation de la souris, Arch. Int. Pharmacodyn. Ther.147:372–387.

    Google Scholar 

  • Boissier, J.-R., Simon, P., and Aron, C., 1968, A new method for rapid screening of minor tranquilizers in mice, Eur. J. Pharmacol.4:145–151.

    PubMed  Google Scholar 

  • Boissier, J.-R., Zebrowska-Lupina, I., and Simon, P., 1972, Profil psychopharmacologique du prazépam, Arch. Int. Pharmacodyn. Ther.196:330–344.

    PubMed  Google Scholar 

  • Boissier, J.-R., Simon, P., and Soubrié, P., 1976, New approaches to the study of anxiety and anxiolytic drugs in animals, in: Proceedings of the Sixth International Congress of Pharmacology, Vol. 3: CNS and Behavioral Pharmacology (M. Airaksinen, ed.), pp. 213–222, Pergamon Press, Oxford.

    Google Scholar 

  • Cannizzaro, G., Nigito, S., Provenzano, P. M., and Vitikova, T., 1972, Modification of depressant and inhibitory action of flurazepam during short-term treatment in the rat, Psychopharmacologia26:173–184.

    PubMed  Google Scholar 

  • Chapman, C. R., and Feather, B. W., 1973, Effects of diazepam on human pain tolerance and pain sensitivity, Psychosom. Med.35:330–340.

    PubMed  Google Scholar 

  • Christensen, J. D., 1973, Tolerance development with chlordiazepoxide in relation to the plasma levels of the parent compound and its main metabolites in mice, Acta Pharmacol. Toxicol.33:262–272.

    Google Scholar 

  • Christmas, A. J., and Maxwell, D. R., 1970, A comparison of the effects of some benzodiazepines and other drugs on aggressive and exploratory behavior in mice and rats, Neuropharmacology9:17–29.

    PubMed  Google Scholar 

  • Collins, P., Sakalis, G., and Minn, F. L., 1976, Clinical response to a potential non-sedative anxiolytic, Curr. Ther. Res.19:512–515.

    PubMed  Google Scholar 

  • Cook, L., and Catania, A. C., 1964, Effects of drugs on avoidance and escape behavior, Fed. Proc. Fed. Am. Soc. Exp. Biol.23:818–835.

    Google Scholar 

  • Cook, L., and Davidson, A. B., 1973, Effects of behaviorally active drugs in a conflict-punishment procedure in rats, in: The Benzodiazepines (S. Garattini, E. Mussini, and L. O. Randall, eds.), pp. 327–345, Raven Press, New York.

    Google Scholar 

  • Cook, L., and Sepinwall, J., 1975a, Psychopharmacological parameters and methods, in: Emotions—Their Parameters and Measurement (L. Levi, ed.), pp. 379–404, Raven Press, New York.

    Google Scholar 

  • Cook, L., and Sepinwall, J., 19756, Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology, Fed. Proc. Fed. Am. Soc. Exp. Biol.34:1889–1897.

    Google Scholar 

  • Cook, L., and Sepinwall, J., 1975c, Behavioral analysis of the effects and mechanisms of action of benzodiazepines, in: Mechanism of Action of Benzodiazepines (E. Costa, and P. Greengard, eds.), pp. 1–28, Raven Press, New York.

    Google Scholar 

  • Cooper, S. J., 1976, Exploratory response habituation and the attenuating effect of an amphetamine-barbiturate mixture, Psychopharmacology49:91–96.

    PubMed  Google Scholar 

  • Costa, E., Guidotti, A., and Mao, C. C., 1976, A GABA hypothesis for the action of benzodiazepines, in: GABA in Nervous System Function (E. Roberts, T. N. Chase, and D. B. Tower, eds.), pp. 413–426, Raven Press, New York.

    Google Scholar 

  • Curtis, D. R., Game, C. J. A., and Lodge, D., 1976, Benzodiazepines and central glycine receptors, Br. J. Pharmacol.56:307–311.

    PubMed  Google Scholar 

  • Dalton, C., Crowley, H. J., Sheppard, H., and Schallek, W., 1974, Regional cyclic nucleotide phosphodiesterase activity in cat central nervous system: effects of benzodiazepines, Proc. Soc. Exp. Biol. Med.145:407–410.

    PubMed  Google Scholar 

  • Dantzer, R., 1975, Étude de l’activité des substances psychotropes sur le comportement de punition du porc, J. Pharmacol. (Paris)6:323–340.

    Google Scholar 

  • Dantzer, R., 1976, Effect of diazepam on performance of pigs in a progressive ratio schedule, Physiol. Behav.17:161–163.

    PubMed  Google Scholar 

  • Dantzer, R., and Roca, M., 1974, Tranquilizing effects of diazepam in pigs subjected to a punishment procedure, Psychopharmacologia40:235–240.

    PubMed  Google Scholar 

  • Davidson, A. B., and Cook, L., 1969, Effects of combined treatment with trifluoperazine-HC1 and amobarbital on punished behavior in rats, Psychopharmacologia15:159–168.

    PubMed  Google Scholar 

  • Davison, M. C., 1970, A choice technique to assess the effects of selective punishment on fixed-ratio performance, J. Exp. Anal. Behav.13:57–64.

    Google Scholar 

  • Dray, A., and Straughan, D. W., 1976, Benzodiazepines: GABA and glycine receptors on single neurons in the rat medulla, J. Pharm. Pharmacol.28:314–315.

    Google Scholar 

  • Foree, D. D., Moretz, F. H., and McMillan, D. E., 1973, Drugs and punished responding II: d-Amphetamine-induced increases in punished responding, J. Exp. Anal. Behav.20:291–300.

    Google Scholar 

  • Fratta, W., Mereu, G., Chessa, P., Paglietti, E., and Gessa, G. L., 1976, Benzodiazepine-induced voraciousness in cats and inhibition of amphetamine anorexia, Life Sci.18:1157–1166.

    PubMed  Google Scholar 

  • Gähwiler, B. H., 1976, Diazepam and chlordiazepoxide: Powerful GABA antagonists in expiants of rat cerebellum, Brain Res.107:176–179.

    PubMed  Google Scholar 

  • Geller, I., 1962, Use of approach avoidance behavior (conflict) for evaluating depressant drugs, in: Psychosomatic Medicine (J. H. Nodine and J. H. Moyer, eds.), pp. 267–274, Lea & Febiger, Philadelphia.

    Google Scholar 

  • Geller, I., and Blum, K., 1970, The effect of 5-HTP on para-chlorophenylalanine (p-CPA) attenuation of “conflict” behavior, Eur. J. Pharmacol.9:319–324.

    PubMed  Google Scholar 

  • Geller, I., and Seifter, J., 1960, The effects of meprobamate, barbiturates, d-amphetamine and promazine on experimentally induced conflict in the rat, Psychopharmacologia1:482–492.

    Google Scholar 

  • Geller, I., and Seifter, J., 1962, Effects of mono-urethans, di-urethans and barbiturates on a punishment discrimination, J. Pharmacol. Exp. Then136:284–288.

    Google Scholar 

  • Geller, I., Bachman, E., and Seifter, J., 1963, Effects of reserpine and morphine on behavior suppressed by punishment, Life Sci.4:226–231.

    PubMed  Google Scholar 

  • Geller, I., Croy, D. J., and Ryback, R. S., 1974a, Effects of ethanol and sodium phenobarbital on conflict behavior of goldfish (Carassius auratus), Pharmacol. Biochem. Behav.2:545–548.

    Google Scholar 

  • Geller, I., Hartmann, R. J., and Croy, D. J., 19746, Attenuation of conflict behavior with cinanserin, a serotonin antagonist: Reversal of the effect with 5-hydroxytryptophan and α-methyltryptamine, Res. Commun. Chem. Pathol. Pharmacol.7:165–174.

    Google Scholar 

  • Glowa, J. R., and Barrett, J. E., 1976, Effects of alcohol on punished and unpunished responding of squirrel monkeys, Pharmacol. Biochem. Behav.4:169–173.

    PubMed  Google Scholar 

  • Goldberg, M. E., and Ciofalo, V. B., 1969, Effect of diphenylhydantoin sodium and chlordiazepoxide alone and in combination on punishment behavior, Psychopharmacologia14:233–239.

    PubMed  Google Scholar 

  • Goldberg, M. E., Manian, A. A., and Efron, D. H., 1966, A comparative study of certain pharmacologic responses following acute and chronic administrations of chlordiazepoxide, Life Sci.6:481–491.

    Google Scholar 

  • Graeff, F. G., 1974, Tryptamine antagonists and punished behavior, J. Pharmacol. Exp. Ther.189:344–350.

    PubMed  Google Scholar 

  • Graeff, F. G., and Schoenfeld, R. I., 1970, Tryptaminergic mechanisms in punished and nonpunished behavior, J. Pharmacol. Exp. Ther.173:277–283.

    PubMed  Google Scholar 

  • Greenblatt, D. J., and Shader, R. I., 1974, Benzodiazepines in Clinical Practice, Raven Press, New York.

    Google Scholar 

  • Haefely, W., Kulcsár, A., Möhler, H., Pieri, L., Polc, P., and Schaffner, R., 1975, Possible involvement of GABA in the central actions of benzodiazepines, in: Mechanism of Action of Benzodiazepines (E. Costa and P. Greengard, eds.), pp. 131–151, Raven Press, New York

    Google Scholar 

  • Haefely, W., Pieri, L., Polc, P., and Schaffner, R., 1976, Benzodiazepines and GABA, Nature (London)263:173–174.

    Google Scholar 

  • Hanson, H. M., and Stone, C.A., 1964, Animal techniques for evaluating antianxiety drugs, in: Animal and Clinical Pharmacologic Techniques in Drug Evaluation (J. H. Nodine and P. E. Siegler, eds.), pp. 317–324, Year Book Medical Publ., Chicago.

    Google Scholar 

  • Hanson, H. M., Witoslawski, J. J., and Campbell, E. H., 1967, Drug effects in squirrel monkeys trained on a multiple schedule with a punishment contingency, J. Exp. Anal. Behav.10:565–569.

    PubMed  Google Scholar 

  • Hendry, D. P., and Van-Toller, C., 1964, Fixed-ratio punishment with continuous reinforcement, J. Exp. Anal. Behav.7:293–300.

    PubMed  Google Scholar 

  • Holtzman, S. G., and Villarreal, J. E., 1969, The effects of morphine on conditioned suppression in rhesus monkeys, Psychon. Sci.17:161–162.

    Google Scholar 

  • Holtzman, S. G., and Villarreal, J. E., 1973, Operant behavior in the morphine-dependent rhesus monkey, J. Pharmacol. Exp. Ther.184:528–541.

    PubMed  Google Scholar 

  • Hoogland, D. R., Miya, T. S., and Bousquet, W. F., 1966, Metabolism and tolerance studies with chlordiazepoxide-2-14C in the rat, Toxicol. Appl. Pharmacol.9:116–123.

    PubMed  Google Scholar 

  • Houser, V. P., 1975, The alteration of aversive thresholds after chronic administration of two tranquilizing agents, Behav. Biol.12:383–392.

    Google Scholar 

  • Houser, V. P., and Paré, W. P., 1973a, Measurement of analgesia using a spatial preference test in the rat, Physiol. Behav.10:535–538.

    Google Scholar 

  • Houser, V. P., and Paré, W. P., 19736, Analgesic potency of sodium salicylate, indometha-cin, and chlordiazepoxide as measured by the spatial preference technique in the rat, Psychopharmacologia32:121–131.

    Google Scholar 

  • Huppert, F. A., and Iversen, S. D., 1975, Response suppression in rats: A comparison of response-contingent and noncontingent punishment and the effect of the minor tranquilizer, chlordiazepoxide, Psychopharmacologia44:67–75.

    PubMed  Google Scholar 

  • Jacobsen, E., 1957, The effect of psychotropic drugs under psychic stress, in: Psychotropic Drugs (S. Garattini and V. Ghetti, eds.), pp. 119–124, Elsevier, Amsterdam.

    Google Scholar 

  • Jefferson, J. W., 1974, Beta-adrenergic receptor blocking drugs in psychiatry, Arch. Gen. Psychiatry31:681–691.

    PubMed  Google Scholar 

  • Kääriäinen, I., 1976, Effects of aminooxyacetic acid and baclofen on the catalepsy and on the increase of mesolimbic and striatal dopamine turnover induced by haloperidol in rats, Acta Pharmacol. Toxicol.39:393–400.

    Google Scholar 

  • Kariya, T., and Aprison, M. H., 1969, Microdetermination of norepinephrine, 3,4-dihydroxyphenylethylamine, and 5-hydroxytryptamine from single extracts of specific rat brain areas, Anal. Biochem.31:102–113.

    PubMed  Google Scholar 

  • Keim, K. L., and Sigg, E. B., 1977, Plasma corticosterone and brain catecholamines in stress: Effect of psychotropic drugs, Pharmacol. Biochem. Behav.6:79–85.

    PubMed  Google Scholar 

  • Kelleher, R. T., and Morse, W. H., 1964, Escape behavior and punished behavior, Fed. Proc. Fed. Am. Soc. Exp. Biol.23:808–817.

    Google Scholar 

  • Kelleher, R. T., and Morse, W. H., 1968, Determinants of the specificity of behavioral effects of drugs, Ergeb. Physiol. Biol. Chem. Exp. Pharmakol.60:1–56.

    Google Scholar 

  • Keller, H. H., Schaffner, R., and Haefely, W., 1976, Interaction of benzodiazepines with neuroleptics at central dopamine neurons, Arch. Pharmacol.294:1–7.

    Google Scholar 

  • Kopin, I. J., Axelrod, J., and Gordon, E., 1961, The metabolic fate of 3H-epinephrine and 14C-metanephrine in the rat, J. Biol. Chem.236:2109–2113.

    PubMed  Google Scholar 

  • Krishnan, G., 1976, Oxprenolol in the treatment of examination stress, Curr. Med. Res. Opinion4:241–243.

    Google Scholar 

  • Lahti, R. A., and Barsuhn, C., 1974, The effect of minor tranquilizers on stress-induced increases in rat plasma corticosteroids, Psychopharmacologia35:215–220.

    PubMed  Google Scholar 

  • Lahti, R. A., and Barsuhn, C., 1975, The effect of various doses of minor tranquilizers on plasma corticosteroids in stressed rats, Res. Commun. Chem. Pathol. Pharmacol.11:595–603.

    PubMed  Google Scholar 

  • Lauener, H., 1963, Conditioned suppression in rats and the effect of pharmacological agents thereon, Psychopharmacologia4:311–325.

    PubMed  Google Scholar 

  • Leander, J. D., McMillan, D. E., and Ellis, F. W., 1976, Ethanol and isopropanol effects on schedule-controlled responding, Psychopharmacology47:157–164.

    Google Scholar 

  • Lehmann, H. E., 1969, Tranquilizers: Clinical insufficiencies and needs, in: The Present Status of Psychotropic Drugs (A. Cerletti and F. J. Bové, eds.), pp. 168–175, Excerpta Medica, Amsterdam.

    Google Scholar 

  • Lehmann, H. E., and Ban, T. A., 1971, Effects of psychoactivé drugs on conflict avoidance behavior in human subjects, Act. Nerv. Super.13:82–85.

    Google Scholar 

  • Margules, D. L., and Stein, L., 1967, Neuroleptics vs. tranquilizers: Evidence from animal studies of mode and site of action, in: Neuro-psychopharmacology (H. Brill, J. O. Cole, P. Deniker, H. Hippius, and P. B. Bradley, eds.), pp. 108–120, Excerpta Medica, Amsterdam.

    Google Scholar 

  • Margules, D. L., and Stein, L., 1968, Increase of “antianxiety” activity and tolerance of behavioral depression during chronic administration of oxazepam, Psychopharmacologia13:74–80.

    PubMed  Google Scholar 

  • Marriott, A. S., and Spencer, P. S. J., 1965, Effects of centrally acting drugs on exploratory behaviour in rats, Br. J. Pharmacol.25:432–441.

    Google Scholar 

  • Masserman, J. H., and Yum, K. S., 1946, An analysis of the influence of alcohol on experimental neurosis in cats, Psychosom. Med.8:36–52.

    PubMed  Google Scholar 

  • McKearney, J. W., 1974, Effects of d-amphetamine, morphine and chlorpromazine on responding under fixed-interval schedules of food presentation or electric shock presentation, J. Pharmacol. Exp. Ther.190:141–153.

    Google Scholar 

  • McKearney, J. W., 1976, Punishment under schedules of stimulus-shock termination: Effects of d-amphetamine and pentobarbital, J. Exp. Anal. Behav.26:281–287.

    PubMed  Google Scholar 

  • McKearney, J. W., and Barrett, J. E., 1975, Punished behavior: Increases in responding after d-amphetamine, Psychopharmacologia41:23–26.

    PubMed  Google Scholar 

  • McMillan, D. E., 1973a, Drugs and punished responding I: Rate-dependent effects under multiple schedules, J. Exp. Anal. Behav.19:133–145.

    Google Scholar 

  • McMillan, D. E., 19736, Drugs and punished responding III: Punishment intensity as a determinant of drug effect, Psychopharmacologia30:61–74.

    Google Scholar 

  • McMillan, D. E., 1973c, Drugs and punished responding IV: Effects of propranolol, ethchlorvynol and chloral hydrate, Res. Commun. Chem. Pathol. Pharmacol.6:167–174.

    Google Scholar 

  • McMillan, D. E., 1975, Determinants of drug effects on punished responding, Fed. Proc. Fed. Am. Soc. Exp. Biol.34:1870–1879.

    Google Scholar 

  • McMillan, D. E., 1976, Drugs and punished responding VI: Body weight as a determinant of drug effects, Res. Commun. Chem. Pathol. Pharmacol.13:1–7.

    PubMed  Google Scholar 

  • McMillan, D. E., and Leander, J. D., 1975, Drugs and punished responding V: Effects of drugs on responding suppressed by response-dependent and response-independent electric shock, Arch. Int. Pharmacodyn. Ther.213:22–27.

    PubMed  Google Scholar 

  • McMillan, D. E., and Leander, J. D., 1976, Changes in the effects of pentobarbital and chlordiazepoxide on punished and unpunished behavior as a function of chronic pentobarbital drinking, Pharmacologist18:235.

    Google Scholar 

  • Meissner, B., and Zeier, H., 1976, Effect of diazepam and Oxprenolol on the conditioned emotional response in the pigeon, Experientia32:780.

    Google Scholar 

  • Miczek, K., 1973a, Effects of scopolamine, amphetamine and chloridiazepoxide on punishment, Psychopharmacologia28:373–389.

    Google Scholar 

  • Miczek, K. A., 1973b, Effects of scopolamine, amphetamine, and benzodiazepines on conditioned suppression, Pharmacol. Biochem. Behav.1:401–411.

    Google Scholar 

  • Miczek, K. A., and Lau, P., 1975, Effects of scopolamine, physostigmine and chlordiazepoxide on punished and extinguished water consumption in rats, Psychopharmacologia42:263–269.

    PubMed  Google Scholar 

  • Millenson, J. R., and Leslie, J., 1974, The conditioned emotional response (CER) as a baseline for the study of anti-anxiety drugs, Neuropharmacology13:1–9.

    PubMed  Google Scholar 

  • Moore, M. S., Tychsen, R. L., and Thompson, D. M., 1976, Extinction-induced mirror responding as a baseline for studying drug effects on aggression, Pharmacol. Biochem. Behav.4:99–102.

    PubMed  Google Scholar 

  • Morrison, C. F., 1969, The effects of nicotine on punished behavior, Psychopharmacologia14:221–232.

    PubMed  Google Scholar 

  • Morrison, C. F., and Stephenson, J. A., 1973, Effects of stimulants on observed behaviour of rats on six operant schedules, Neuropharmacology12:297–310.

    PubMed  Google Scholar 

  • Morse, W. H., 1964, Effect of amobarbital and chlorpromazine on punished behavior in the pigeon, Psychopharmacologia6:286–294.

    PubMed  Google Scholar 

  • Naess, K., and Rasmussen, E. W., 1958, Approach-withdrawal responses and other specific behavior reactions as screening test for tranquilizers, Acta Pharmacol. Toxicol.15:99–114.

    Google Scholar 

  • Noble, W., and Delini-Stula, A., 1976, Effect of Oxprenolol on some fear-induced behavioral responses and hyperthermia in rats subjected to inescapable shocks, Psycho-pharmacology49:17–22.

    Google Scholar 

  • Nolan, N. A., and Parkes, M. W., 1973, The effects of benzodiazepines on the behavior of mice on a hole-board, Psychopharmacologia29:277–288.

    PubMed  Google Scholar 

  • Pekkarinen, A., 1970, The inhibitory effect of thymoleptic antidepressants on the neurogenic increase of the corticosteroid content of the rat plasma, Acta Pharmacol. Toxicol.28(Suppl. 1):71.

    Google Scholar 

  • Polc, P., and Haefely, W., 1976, Effects of two benzodiazepines, phenobarbitone, and baclofen on synaptic transmission in the cat cuneate nucleus, Arch. Pharmacol.294:121–131.

    Google Scholar 

  • Poschel, B. P. H., 1971, A simple and specific screen for benzodiazepine-like drugs, Psychopharmacologia19:193–198.

    PubMed  Google Scholar 

  • Poschel, B. P. H., McCarthy, D. A., Chen, G., and Ensor, C. R., 1974, Pyrazapon (CI-683): A new antianxiety agent, Psychopharmacologia35:257–271.

    PubMed  Google Scholar 

  • Quenzer, L. F., Feldman, R. S., and Moore, J. W., 1974, Toward a mechanism of the antiaggression effects of chlordiazepoxide in rats, Psychopharmacologia34:81–94.

    PubMed  Google Scholar 

  • Randall, L. O., and Kappell, B., 1973, Pharmacological activity of some benzodiazepines and their metabolites, in: The Benzodiazepines (S. Garattini, E. Mussini, and L. O. Randall, eds.), pp. 27–51, Raven Press, New York.

    Google Scholar 

  • Randall, L. O., Schallek, W., Heise, G. A., Keith, E. F., and Bagdon, R. E., 1960, The psychosedative properties of methaminodiazepoxide, J. Pharmacol. Exp. Ther.129:163–171.

    PubMed  Google Scholar 

  • Randall, L. O., Schallek, W., Sternbach, L. H., and Ning, R. Y., 1974, Chemistry and pharmacology of the 1,4-benzodiazepines, in: Psychopharmacological Agents, Vol. III (M. Gordon, ed.), pp. 175–281, Academic Press, New York.

    Google Scholar 

  • Richalle, M., 1969, Combined action of diazepam and d-amphetamine on fixed interval performance in cats, J. Exp. Anal. Behav.12:989–998.

    Google Scholar 

  • Robichaud, R. C., and Sledge, K. L., 1969, The effects of p-chlorophenylalanine on experimentally induced conflict in the rat, Life Sci.8:965–969.

    PubMed  Google Scholar 

  • Robichaud, R. C., Sledge, K. L., Hefner, M. A., and Goldberg, M. E., 1973, Propranolol and chlordiazepoxide on experimentally induced conflict and shuttle box performance in rodents, Psychopharmacologia32:157–160.

    PubMed  Google Scholar 

  • Rushton, R., Steinberg, H., and Tomkiewicz, M., 1973, Effects of chlordiazepoxide alone and in combination with amphetamine on animal and human behavior, in: The Benzodiazepines (S. Garattini, E. Mussini, and L. O. Randall, eds.), pp. 355–366, Raven Press, New York.

    Google Scholar 

  • Sanger, D. J., and Blackman, D. E., 1975, The effects of tranquilizing drugs on timing behaviour in rats, Psychopharmacologia44:153–156.

    PubMed  Google Scholar 

  • Sansone, M., 1975, Benzodiazepines and amphetamine on avoidance behaviour in mice, Arch. Int. Pharmacodyn. Ther.218:125–132.

    PubMed  Google Scholar 

  • Schanberg, S. M., Schildkraut, J. J., and Kopin, I. J., 1967a, The effects of pentobarbital on the fate of intracisternally administered norepinephrine-H3, J. Pharmacol. Exp. Ther.157:311–318.

    Google Scholar 

  • Schanberg, S. M., Schildkraut, J. J., and Kopin, I. J., 19676, The effects of psychoactive drugs on norepinephrine-3H metabolism in brain, Biochem. Pharmacol.16:393–399.

    Google Scholar 

  • Scheckel, C. L., 1970, Preclinical psychopharmacology, in: Principles of Psychopharmacology (W. G. Clark and J. del Giudice, eds.), pp. 235–253, Academic Press, New York.

    Google Scholar 

  • Schlosser, W., 1971, Action of diazepam on the spinal cord, Arch. Int. Pharmacodyn. Ther.194:93–102.

    PubMed  Google Scholar 

  • Schmidt, R. F., Vogel, M. E., and Zimmermann, M., 1967, Die Wirkung von Diazepam auf die präsynaptische Hemmung und andere Ruckenmarksreflexe, Arch. Pharmacol.258:69–82.

    Google Scholar 

  • Schoenfeld, R. I., 1976, Lysergic acid diethylamide- and mescaline-induced attenuation of the effect of punishment in the rat, Science192:801–803.

    PubMed  Google Scholar 

  • Sepinwall, J., Grodsky, F. S., Sullivan, J. W., and Cook, L., 1973, Effects of propranolol and chlordiazepoxide on conflict behavior in rats, Psychopharmacologia31:375–382.

    PubMed  Google Scholar 

  • Sepinwall, J., Sullivan, J. W., Mitchell, D. N., and Cook, L., 1976, Effects of benzodiazepine antianxiety agents on punished (conflict) and unpunished behavior in drug-naive rats, Fed. Proc. Fed. Am. Soc. Exp. Biol.35:268.

    Google Scholar 

  • Soubrié, P. Schoonhoed, L., Simon, P., and Boissier, J. R., 1972, Conflict behavior in a heated-floor maze: Effects of oxazepam, Psychopharmacologia26:317–320.

    PubMed  Google Scholar 

  • Soubrié, P., Wlodaver, C., Schoonhoed, L., Simon, P., and Boissier, J. R., 1974, Preselection of animals in studies of antianxiety drugs, Neuropharmacology13:719–728.

    PubMed  Google Scholar 

  • Soubrié, P., Simon, P., and Boissier, J. R., 1975a, Newer or more operational models and/or methods for studying antianxiety drugs in animals, in: Neuro-psychopharmacology (J. R. Boissier, H. Hippius, and P. Pichot, eds.), pp. 720–728, Excerpta Medica, Amsterdam.

    Google Scholar 

  • Soubrié, P., Kulkarni, S., Simon, P., and Boissier, J. R., 1975b, Effets des anxiolytiques sur la prise de nourriture de rats et de souris placés en situation nouvelle ou familière, Psychopharmacologia45:203–210.

    Google Scholar 

  • Stein, L., Wise, C. D., and Berger, B. D., 1973, Antianxiety action of benzodiazepines: Decrease in activity of serotonin neurons in the punishment system, in: Benzodiazepines (S. Garattini, E. Mussini, and L. O. Randall, eds.), pp. 299–326, Raven Press, New York.

    Google Scholar 

  • Stein, L., Wise, C. D., and Belluzzi, J. D., 1975, Effects of benzodiazepines on central serotonergic mechanisms, in: Mechanism of Action of Benzodiazepines (E. Costa, and P. Greengard, eds.), pp. 29–44, Raven Press, New York.

    Google Scholar 

  • Steiner, F. A., and Felix, D., 1976a, Antagonistic effects of GABA and benzodiazepines on vestibular and cerebellar neurons, Nature (London)260:346–347.

    Google Scholar 

  • Steiner, F. A., and Felix, D., 1976b, Reply, Nature (London)263:174.

    Google Scholar 

  • Stitzer, M., 1974, Comparison of morphine and chlorpromazine effects on moderately and severely suppressed punished responding in the pigeon, J. Pharmacol. Exp. Ther.191:172–178.

    PubMed  Google Scholar 

  • Tamura, M., 1963, The effects of some central nervous system depressants on conflict behavior in dogs, Jpn. J. Pharmacol.13:133–142.

    PubMed  Google Scholar 

  • Thiébot, M.-H., Soubrié, P., Simon, P., and Boissier, J.-R., 1976, Spécificité d’action des tranquillisants mineurs dans le test de l’escalier: Relation entre ces effets et leurs propriétés anxiolytiques, J. Pharmacol. (Paris)7:87–102.

    Google Scholar 

  • Thompson, D. M., 1972, Enhancement of progressive-ratio performance by chlordiazepox-ide and phenobarbital, J. Exp. Anal. Behav.17:287–292.

    PubMed  Google Scholar 

  • Ts’o, T. O. T., and Chenoweth, M. B., 1976, Comparison between chronic chlordiazepox-ide treatment and shock removal in a conflict situation in rats, Neuropharmacology15:99–101.

    PubMed  Google Scholar 

  • Tye, N. C., Nicholas, D. J., and Morgan, M. J., 1975, Chlordiazepoxide and preference for free food in rats, Pharmacol. Biochem. Behav.3:1149–1151.

    PubMed  Google Scholar 

  • Tyrer P. J., and Lader, M. H., 1974a, Response to propranolol and diazepam in somatic and psychic anxiety, Br. Med. J.2:14–16.

    Google Scholar 

  • Tyrer, P. J., and Lader, M. H., 19746, Physiological and psychological effects of ±- propranolol, + -propranolol and diazepam in induced anxiety, Br. J. Clin. Pharmacol.1:379–385.

    Google Scholar 

  • Vogel, J. R., Beer, B., and Clody, D. E., 1971, A simple and reliable conflict procedure for testing anti-anxiety agents, Psychopharmacologia21:1–7.

    PubMed  Google Scholar 

  • Vogel-Sprott, M., 1967, Alcohol effects on human behavior under reward and punishment, Psychopharmacologia11:337–344.

    PubMed  Google Scholar 

  • Vorne, M. S., Puolakka, J. O., and Idänpään-Heikkilä, J. E., 1975, Diazepam, ethanol and drug metabolizing enzymes in rat liver, Arch. Int. Pharmacodyn. Ther.216:280–287.

    PubMed  Google Scholar 

  • Warner, R. S., 1965, Management of the office patient with anxiety and depression, Psychosomatics6:347–351.

    PubMed  Google Scholar 

  • Wedeking, P. W., 1973, Comparison of chlordiazepoxide and food deprivation in rats on a fixed-ratio satiation schedule, Physiol. Behav.10:707–710.

    PubMed  Google Scholar 

  • Wedeking, P. W., 1974, Schedule-dependent differences among anti-anxiety drugs, Pharmacol. Biochem. Behav.2:465–472.

    PubMed  Google Scholar 

  • Weinryb, I., Beer, B., Chasin, M., Proctor, E. B., and Hess, S. M., 1975, Studies in vitro and in vivo with SQ-20,009: An inhibitor of cyclic nucleotide phosphodiesterase with central nervous system activity, in: Neuropsychopharmacology (J. R. Boissier, H. Hippius, and P. Pichot, eds.), pp. 857–865, Excerpta Medica, Amsterdam.

    Google Scholar 

  • Weis, J., 1969, Morphine antagonistic effect of chlordiazepoxide (Librium®), Experientia25:381.

    PubMed  Google Scholar 

  • Weller, C. P., Ibrahim, I., and Sulman, F. G., 1968, Analgesic profile of tranquilizers in multiple screening tests in mice, Arch. Int. Pharmacodyn. Ther.176:176–192.

    PubMed  Google Scholar 

  • Winter, J. C., 1972, Comparison of chlordiazepoxide, methysergide, and cinanserin as modifiers of punished behavior and as antagonists of N,N-dimethyltryptamine, Arch. Int. Pharmacodyn. Ther.197:147–159.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Wuttke, W., and Kelleher, R. T., 1970, Effects of some benzodiazepines on punished and unpunished behavior in the pigeon, J. Pharmacol. Exp. Ther.172:397–405.

    PubMed  Google Scholar 

  • Yen, H. C. Y., Krop, S., Mendez, H. C., and Katz, M. H., 1970, Effects of some psychoactive drugs on experimental “neurotic” (conflict induced) behavior in cats, Pharmacology3:32–40.

    PubMed  Google Scholar 

  • Young, A. B., Zukin, S. R., and Snyder, S. H., 1974, Interaction of benzodiazepines with central nervous glycine receptors: Possible mechanism of action, Proc. Natl. Acad. Sci. U.S.A.71:2246–2250.

    PubMed  Google Scholar 

  • Zakusov, V. V., Ostrovskaya, R. U., Markovitch, V. V., Molodavkin, G. M., and Bulayev, V. M., 1975, Electrophysiological evidence for an inhibitory action of diazepam upon cat brain cortex, Arch. Int. Pharmacodyn. Ther.214:188–205.

    PubMed  Google Scholar 

  • Zbinden, G., and Randall, L. O., 1967, Pharmacology of benzodiazepines: Laboratory and clinical correlations, Adv. Pharmacol. Chemother.5:213–291.

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Research Division, Hoffmann-La Roche Inc., Nutley, New Jersey, 07110, USA

    Jerry Sepinwall & Leonard Cook

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  1. Jerry Sepinwall
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  2. Leonard Cook
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  1. Department of Pharmacology, University of Cambridge, UK

    Leslie L. Iversen

  2. Department of Psychology, University of Cambridge, UK

    Susan D. Iversen

  3. Departments of Pharmacology and Psychiatry, School of Medicine, The Johns Hopkins University, USA

    Solomon H. Snyder

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Sepinwall, J., Cook, L. (1978). Behavioral Pharmacology of Antianxiety Drugs. In: Iversen, L.L., Iversen, S.D., Snyder, S.H. (eds) Handbook of Psychopharmacology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-3189-6_6

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  • DOI: https://doi.org/10.1007/978-1-4684-3189-6_6

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