Abstract
Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other.
The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Babbini, M., Gaiardi, M., Bartoletti, M., Torrielli, M. V., De Marchi, F.: The conflict behavior in rats for the evaluation of a homogeneous series of 3-hydroxybenzodiazepines: structureactivity relationships. Pharmacol. Res. Commun. 7, 337–346 (1975)
Babbini, M., Gaiardi, M., Bartoletti, M.: Changes in operant behavior as an index of withdrawal state from morphine in rats. Psychon. Sci. 29, 142–144 (1972)
Babbini, M., Torrielli, M. V., Gaiardi, M., Bartoletti, M., De Marchi, F.: Influence of N1-2-hydroxyethyl substitution on central activity of oxazepam and lorazepam. Pharmacology 10, 345–353 (1973)
Biel, H. J., Bopp, B.: Antidepressant drugs. In: Medicinal chemistry, M. Gordon, ed., Vol. 4-III, pp. 283–341. New York: Academic Press 1974
Blum, K.: Effects of chlordiazepoxide and pentobarbital on conflict behavior in rats. Psychopharmacologia (Berl.) 17 391–398 (1970)
Blum, J. E., Hürlimann, A.: The effect of psycotropic drugs on the occurrence of stress-induced gastric ulcers. Med. Psicosom. 13, 250–254 (1968)
Cook, L., Davidson, A. B.: 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, New York: Raven Press 1973
Finney, D. J.: Probit analysis. Cambridge University Press 1971
Geller, I.: Relative potencies of benzodiazepines as measured by their effects on conflict behavior. Arch. int. Pharmacodyn. 149, 243–247 (1964)
Geller, I., Beckman, E., Seifter, J.: Effects of reserpine and morphine on behavior suppressed by punishment. Life Sci. 4, 226 (1963)
Geller, I., Kulak, J. T., Jr., Seifter, J.: The effects of chlordiazepoxide and chlorpromazine on a punishment discrimination. Psychopharmacologia (Berl.) 3, 374–385 (1962)
Geller, I., Seifter, J.: The effects of meprobamate, barbiturates, d-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia (Berl.) 1, 482–492 (1960)
Haider, I.: A comparative trial of Ro 4-6270 and amitriptyline in depressive illness. Brit. J. Psychiat. 113, 993–998 (1967)
Houck, J. E.: Combined therapy in anxiety-depressive syndromes. In: Diseases of the nervous system, Vol. 31, pp. 269–273 (1970)
Margules, D. L., Stein, L.: Increase of antianxiety activity and tolerance of behavioral depression during administration of oxazepam. Psychopharmacologia (Berl.) 13, 74–80 (1968)
Nakajima, R., Take, Y., Moriya, R., Saji, Y., Yui, Z., Nagawa, Y.: Pharmacological studies on new potent central depressants, 8-chloro-6-phenyl-4 H-s-triasolo [4,3a] [1,4] benzodiazepine (D-40 TA) and its l-methyl analogue (D-65 MT). Jap. J. Pharmacol. 21, 497–519 (1971)
Smith, M.: Clinical response to amitriptyline and chlordiazepoxide-amitriptyline (Limbitrol) in anxiety-depressive states. Psychosomatics 14, 168–175 (1973)
Stark, P., Turk, J. A., Redman, C. E., Henderson, J. K.: Sensitivity and specificity of positive reinforcing areas to neurosedatives, antidepressants and stimulants. J. Pharmacol. exp. Ther. 166, 163–169 (1969)
Stein, L., Berger, B. D.: Psychopharmacology of 7-chloro-5-(ochlorophenyl)-1,3-dihydro-3-hydroxy-2H-1,4-benzodiazepin-2-one (Lorazepam) in squirrel monkey and rat. Arzneimittel-Forsch. 21, 1073–1078 (1971)
Stein, L., Wise, C. D., Berger, B. D.: Antianxiety action of benzodiazepines: decrease in activity of serotonin neurons in the punishment system. In: The benzodiazepines, S. Garattini, E. Mussini, and L. O. Randall, eds., pp. 299–326. New York: Raven Press 1973
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Babbini, M., Gaiardi, M. & Bartoletti, M. Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats. Psychopharmacology 48, 251–254 (1976). https://doi.org/10.1007/BF00496857
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00496857