Abstract
The possible participation of the cholinergic synapses of the hippocampus in the regulation of the learning process was investigated by observing the effect of an intrahippocampal injection of the muscarinolytic atropine on acquisition, consolidation, and extinction.
Male Wistar rats were trained for a shock motivated brightness discrimination in a semi-automatic Y-maze. The training was non-stop and continued till the subjects reached the training criterion of performing 10 consecutive runs correctly.
The pre-training application of atropine impairs the learning ability significantly, but produces a considerable improvement of retention as compared to the controls. The post-training application of the same dose also produces a considerable improvement of retention. However, when atropine is given 1 min before the first extinction test, no significant effect is observed.
It is assumed that atropine has two distinct effects: whereas on one hand it impairs acquisition, i.e., has an aversive effect on short-term memory related processes, on the other hand it has a positive effect on consolidation. It is concluded that atropine has different effects on the various phases of learning. This may be due to changes occurring in cholinergic neuronal activity of the hippocampus during training.
Similar content being viewed by others
References
Barrett, R. J., Leith, N. J., Ray, O. R.: Permanent facilitation of avoidance behavior by (d-amphetamine and scopolamine. Psychopharmacologia (Berl.) 25, 321–331 (1972)
Barrett, R. J., Leith, N. J., Ray, O. R.: A behavioral and pharmacological analysis of variables mediating active-avoidance behavior in rats. J. comp. physiol. Psychol. 82, 489–500 (1973)
Berger, B. D., Stein, L.: An analysis of the learning deficits produced by scopolamine. Psychopharmacologia (Berl.) 14, 271–283 (1969)
Bignami, G., Rosic, N.: The nature of disinhibitory phenomena caused by central cholinergic (muscarinic) blockade. In: Advances in Neuropsychopharmacology. O. Vinar, Z. Votava, and P. B. Bradley, Eds., pp. 481–496 Amsterdam: North-Holland Publ. and Prague: Czechoslovak Medical Press 1971
Bignami, G., Amorico, L., Frontali, M., Rosic, N.: Central cholinergic blockade and two-way avoidance inhibition: The role of response disinhibition. Physiol. Behav. 7, 461–470 (1971)
Bignami, G., Rosic, N.: Acquisition and performance effects of scopolamine and of treatment withdrawal in avoidance situations. Physiol. Behav. 8, 1127–1134 (1972)
Bures, J.: The effect of atropine and physostigmine on some behavioral and electrophysiological functions in the rat. Progr. Brain Res. 28, 61–72 (1968)
Buresova, O., Bures, J., Bohdanecky, Z., Weiss, T.: Effect of atropine on learning, extinction, retention and retrieval in rats. Psychopharmacologia (Berl.) 5, 255–263 (1964)
Bohdanecky, Z., Jarvik, E. M.: Impairment of one trial passive avoidance learning in mice by scopolamine, scopolamine methylbromide and physostigmine. Int. J. Neuropharmacol. 6, 217–222 (1967)
Carlton, P. L.: Cholinergic mechanisms in the control of behavior by the brain. Psychol. Rev. 70, 19–39 (1963)
Carlton, P. L.: Cholinergic mechanism in the control of behavior. In: Psychopharmacology: A Review of Progress. 1957–1967. D. H. Efron (Editor-in-Chief). pp. 125–135. Washington: Public Health Service Publications, No. 1836, 1968
Clark, C. V. H.: Effect of hippocampal and neocortical ablation on scopolamine-induced activity in the rat. Psychopharmacologia (Berl.) 17, 289–301 (1970)
Deutsch, J. A.: The cholinergic synapse and the site of memory. Science 174, 788–794 (1971)
Douglas, R. J.: The hippocampus and behavior. Psychol. Bull. 67, 416–442 (1967)
Evangelista, A. M., Izquierdo, I.: The effect of pre- and post-trial amphetamine injections on avoidance response of rats. Psychopharmacologia (Berl.) 20, 42–47 (1971)
Evangelista, A. M., Izquierdo, I.: Effects of atropine on avoidance conditioning: Interactions with atropine and comparison with N-methyl-atropine. Psychopharmacologia (Berl.) 9, 241–248 (1972)
Fifkova, E., Marsala, J.: Stereotaxic atlases for the cat, rabbit and rat. In: Electrophysiological Methods in Biological Research, Jan Bures, Mojmir Petran, and Josef Zachar. Eds., Prague: Publishing House of the Czechoslovak Academy of Sciences 1960
Glassman, E.: The biochemistry of learning: An evaluation of the role of RNA and protein. Ann. Rev. Biochem. 38, 605–646 (1969)
Herz, A.: Drug and conditioned avoidance response. Int. Rev. Neurobiol. 2, 229–277 (1960)
Herz, A.: Some actions of cholinergic and anticholinergic drugs on reactive behavior. Progr. Brain Res. 28, 73–89 (1968)
Hyden, H.: RNA in brain cells. In: The Neurosciences: A study Programm, Quarton G. C., Melnechuk, T., Schmitt, F. O., Eds., pp. 248–266. New York: Rockefeller University Press 1971
Ilyutchenok, R. Y.: Involvement of cholinergic structures of the limbic system and reticular system in the mechanism of memory: Pharmacological aspects. Ergebn. exp. Med. 10, 121–128 (1972)
Izquierdo, I.: Hippocampal physiology: Experiments on regulation of its electrical activity, on the mechanism of seizures and on a hypothesis of learning. Behav. Biol. 7, 669–698 (1972)
Jacobson, E., Sonne, E.: The effects of benzilic acid diethylaminoethylester HC 2 (Benactyzine) on stress-induced behavior in the rat. Acta pharmacol (Kbh.) 11, 135–142 (1955)
Khavari, K. A., Maickel, R. P.: Atropine and atropine methyl bromide effects on behavior of rats. Int. J. Neuropharmacol. 6, 301–306 (1967)
Leaf, R. C., Miller, S. A.: Effects of scopolamine on operant avoidance acquisition and retention. Psychopharmacologia (Berl.) 9, 101–109 (1966)
Matthies, H., Lö\ner, B., Ott, T., Rauca, Ch., Pohle, W.: The intraneuronal regulation of neuronal connectivity. In: Brain, Nerves and Synapses, Bloom, F. E., and Acheson, G. H., Eds., Vol. 4 of the Proceedings, 5th International Congress of Pharmacology, pp. 29–38. Basel: Karger 1973
McCoy, D. F.: Some effects of scopolamine on acquisition and extinction performance in rats. Psychol. Rep. 30, 867–873 (1972)
McGaugh, J. L.: Drug facilitation of learning and memory. Ann. Rev. Pharmacol. 13, 229–241 (1973)
Meyers, B., Roberts, K. H., Riciputi, R. H., Domino, E. F.: Some effects of muscarinic cholinergic blocking drugs on behavior and electrocorticogram. Psychopharmacologia (Berl.) 5, 289–300 (1964)
Michelson, M. J.: Pharmacological evidence of the role of acetylcholine in the higher nervous activity of man and animals. Activ. nerv. sup. (Praha) 3-2, 140–147 (1961)
Olds, J.: Learning and the hippocampus. Rev. Canad. Biol. 31, Suppl. 225–238 (1972)
Oliverio, A.: Neurohumoral systems and learning. In: Psychopharmacology: A Review of Progress, 1957–1967. D. H. Efron (Editor-in-Chief), pp. 867–878. Washington: Public Health Service Publications No. 1836, 1968
Ott, T., Dosske, A., Thiemann, W., Matthies, H.: Eine teilautomatische Lernanlage für optische Diskriminierungsreaktionen mit Ratten. Acta biol. med. germ. 29, 103–108 (1972)
Ott, T., Matthies, H.: Some effects of RNA precursors on development and maintenance of long-term memory: hippocampal and cortical pre- and post-training application of RNA precursors. Psychopharmacologia (Berl.) 28, 195–204 (1973)
Ott, T., Krug, M., FÄhse, Chr., Matthies, H.: Time dependent effects of ECS, cortical and hippocampal. spreading depression on consolidation. Ergebn. exp. Med. (in press)
Pohle, W., Matthies, H.: The incorporation of 3H-uridine monophosphate into the rat brain during the training period: a microautoradiographic study. Brain Res. 29, 123–127 (1971)
Renfro, C. T., Freedman, P. E., Rosen, A. J.: The concurrent effects of scopolamine on spontaneous motor activity and the acquisition of an active avoidance response. Neuropharmacology 11, 337–346 (1972)
Russeil, R. W.: Behavioral aspects of cholinergic transmission. Fed. Proc. 28, 121–131 (1969)
Scoville, W. B., Millner, B.: Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiat. 20, 11–21 (1957)
Segal, M.: Flow of conditioned responses in limbic telencephalic system of the rat. J. Neurophysiol. 36, 840–834 (1973)
Shute, C. C. D., Lewis, P. R.: The ascending cholinergic reticular system: neocortical olfactory and subcortical projections. Brain 90, 497–520 (1967)
Suits, E., Isaacson, R. C.: The effects of scopolamine hydrobromide on one-way and two-way avoidance learning in rats. Int. J. Neuropharmacol. 7, 441–446 (1968)
Vinogradova, O. S.: Registration of information in the limbic system. In: Shortterm Changes in Neuronal Activity and Behavior. Horn, G., and Hinde, R. A., Eds., pp. 95–140. Cambridge: Cambridge University Press 1970
Warburton, D. M.: Behavioral effects of central and peripheral changes in acetylcholine systems. J. comp. physiol. Psychol. 68, 56–64 (1969)
Warburton, D. M., Russel, R. W.: Some behavioral effects of cholinergic stimulation in the hippocampus. Life Sci. 8, 617–627 (1969)
Warburton, D. M., Brown, K.: Attenuation of stimulus sensitivity induced by scopolamine. Nature. (Lond.) 230, 126–127 (1971)
Whitehouse, J. M.: Effects of atropine on discrimination learning in the rat. J. comp. physiol. Psychol. 57, 13–15 (1964)
Whitehouse, J. M.: The effects of physostigmine on discrimination learning. Psychopharmacologia (Berl.) 9, 183–188 (1966)
Author information
Authors and Affiliations
Additional information
The research was supported by the grants of the Ministerium für Wissenschaft und Technik der DDR.
The paper forms a part of the post-graduate thesis of the first author.
Rights and permissions
About this article
Cite this article
Singh, H.K., Ott, T. & Matthies, H. Effect of intrahippocampal injection of atropine on different phases of a learning experiment. Psychopharmacologia 38, 247–258 (1974). https://doi.org/10.1007/BF00421377
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00421377