Summary
Atropine or scopolamine improved conditioned avoidance behavior for most rats which performed poorly, in spite of extensive training, in a shuttle-box procedure. As previously reported, d-amphetamine also improved performance in many of these animals, but there was no particular relationship between a rat's responses to the cholinergic blocking agents and to d-amphetamine. The effect of any one of the 3 agents was, for the most part, reversible after the drug effect had dissipated.
Physostigmine was quite potent in disrupting avoidance behavior in rats that performed well in the shuttle-box, even in animals that were overtrained. This impairment was antagonized by atropine or scopolamine, partly antagonized by d-amphetamine, and not antagonized by methyl atropine. Poor performers were found to be very sensitive to the disruptive effects of physostigmine, losing much of their escape behavior after relatively small doses.
The results are interpreted as evidence for a central cholinergic system with inhibitory influences for modulating stimulus-response patterns. Under normal circumstances this inhibitory system probably functions in an integrated manner with the adrenergic mobilizing system for the central control of learned behavior. Centrally-active anticholinergic drugs of the muscarinic type appear to influence behavioral responses by inducing a response disinhibition.
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References
Bignami, G.: Effects of benactyzine and adiphenine on instrumental avoidance conditioning in a shuttle-box. Psychopharmacologia (Berl.) 5, 264–279 (1964).
-Anticholinergic agents as tools in the investigation of behavioral phenomena. Paper presented at V. Int. Cong. of the Collegium Internationale Neuro-Psycho-pharmacologicum, Washington, D.C.; Mar. 28–31, 1966.
Bohdanecký, Z., and M. Jarvik: Impairment of one-trial passive avoidance learning in mice by scopolamine, scopolamine methylbromide and physostigmine. Int. J. Neuropharmacol. 6, 217–222 (1967).
Bureš, J., Z. Bohdanecký, and T. Weiss: Physostigmine induced hippocampal theta activity and learning in rats. Psychopharmacologia (Berl.) 3, 254–263 (1962).
Burešova, O., Z. Bohdanecký, J. Bureš, and T. Weiss: Effect of pharmacologically induced synchronization of cortical or hippocampal activity on learning in rats. In: Pharmacology of conditioning, learning and retention, pp. 351–356. New York: The Macmillan Co. 1965.
Carlton, P. L.: Cholinergic mechanisms in the control of behavior by the brain. Psychol. Rev. 70, 19–39 (1963).
—: Scopolamine, amphetamine and light-reinforced responding. Psychon. Sci. 5, 347–348 (1966).
Deutsch, J. A., and D. Deutsch: Physiological Psychology, pp. 220–221. Home-wood, Ill.: The Dorsey Press 1966.
—, and H. Lutzky: Memory enhancement by anti-cholinesterase as a function of initial learning. Nature (Lond.) 213, 742 (1967).
Douglas, R. J.: The hippocampus and behavior. Psychol. Bull. 67, 416–442 (1967).
—, and R. L. Isaacson: Spontaneous alternation and scopolamine. Psychon. Sci. 4, 283–284 (1966).
Erickson, C. K., and R. K. Chalmers: Hippocampal theta rhythm during avoidance blockade. Pharmacologist 8, 218 (1966).
Goodman, L. S., and A. Gilman: The pharmacological basis of therapeutics, 3rd edit. New York: The Macmillan Co. 1965.
Herz, A.: Die Bedeutung der Bahnung für die Wirkung von Scopolamin und ähnlichen Substanzen auf bedingte Reaktionen. Z. Biol. 112, 104–112 (1960).
Isaacson, R. L., R. J. Douglas, and R. Y. Moore: The effect of radical hippocampal ablation on acquisition of avoidance response. J. comp. physiol. Psychol. 54, 625–628 (1961).
—, and W. O. Wickelgren: Hippocampal ablation and passive avoidance. Science 138, 1104–1106 (1962).
Leaf, R. C., and S. A. Muller: Effects of scopolamine on operant avoidance acquisition and retention. Psychopharmacologia (Berl.) 9, 101–109 (1966).
Longo, V. G.: Behavioral and electroencephalographic effects of atropine and related compounds. Pharmacol. Rev. 18, 965–996 (1966).
McCleary, R. A.: Response-modulating functions of the limbic system: initiation and suppression. In: Progress in Physiological Psychology, Vol. 1. New York: Academic Press 1966.
McNew, J. J., and R. Thompson: Role of the limbic system in active and passive avoidance conditioning in the rat. J. comp. physiol. Psychol. 61, 173–180 (1966).
Meyers, B.: Some effects of scopolamine on a passive avoidance response in rats. Psychopharmacologia (Berl.) 8, 111–119 (1965).
—, and E. F. Domino: The effects of cholinergic blocking drugs on spontaneous alternation in rats. Arch. int. Pharmacodyn. 150, 525–529 (1964).
—, K. H. Roberts, R. H. Riciputi, and E. F. Domino: Some effects of muscarinic cholinergic blocking drugs on behavior and the electroencephalogram. Psycho-pharmacologia (Berl.) 5, 289–300 (1964).
Moore, K. E., and R. H. Rech: Antagonism by monoamine oxidase inhibitors of α-methyltyrosine-induced catecholamine depletion and behavioral depression. J. Pharmacol. exp. Ther. 156, 70–75 (1967).
Niki, H.: The effects of hippocampal ablation on the behavior in the rat. Jap. Psychol. Res. 4, 139–153 (1962).
Oliverio, A.: Contrasting effects of scopolamine on mice trained simultaneously with two different schedules of avoidance conditioning. Psychopharmacologia (Berl.) 11, 39–51 (1967).
Parkes, M. W.: An examination of central actions characteristic of scopolamine: comparison of central and peripheral activity in scopolamine, atropine and some synthetic basic esters. Psychopharmacologia (Berl.) 7, 1–19 (1965).
Pfeiffer, C. C., and E. H. Jenney: The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain. Ann. N. Y. Acad. Sci. 66, 753–764 (1957).
Rech, R. H.: Antagonism of reserpine behavioral depression by d-amphetamine. J. Pharmacol. exp. Ther. 146, 369–376 (1964).
—: Amphetamine effects on poor performance of rats in a shuttle-box. Psychophar-macologia (Berl.) 9, 110–117 (1966).
—, H. K. Borys, and K. E. Moore: Alterations in behavior and brain catecholamine levels in rats treated with α-methyltyrosine. J. Pharmacol. exp. Ther. 153, 412–419 (1966).
Stein, L.: Amphetamine and neural reward systems. In: Animal behavior and drug action, pp. 91–118. Boston: Little, Brown and Co. 1964.
Stone, G. C.: Effects of drugs on avoidance behavior. II. Individual differences in susceptibilities. Psychopharmacologia (Berl.) 7, 283–302 (1965).
Stratton, L. O., and L. Petrinovich: Post-trial injections of anticholinesterase drug and maze learning in two strains of rats. Psychopharmacologia (Berl.) 5, 47–54 (1963).
Whitehouse, J. A.: The effects of physostigmine on discrimination learning. Psychopharmacologia (Berl.) 9, 183–188 (1966).
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This investigation was supported by USPHS Grant MH 11469.
I wish to thank Mrs. Dorothy Farrar and Mrs. Kathryn Grube for technical assistance.
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Rech, R.H. Effects of cholinergic drugs on poor performance of rats in a shuttle-box. Psychopharmacologia 12, 371–383 (1968). https://doi.org/10.1007/BF00401343
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DOI: https://doi.org/10.1007/BF00401343