Summary
A method for the quantification of the effects of drugs upon the EEG and the EEG activating response using an Offner frequency analyser has been presented. The activating response has been shown to be graded in three respects: (1) latency of onset, (2) degree of depression of certain brain waves, and (3) degree of acceleration of frequency of certain brain waves. Using the degree of depression of activity of brain waves in the frequency range of 1.5 to 3.5 c.p.s. by graded stimuli to the midbrain reticular formation, it was possible to obtain estimates of the effect of drugs on the excitability and reactivity of the activating response. Simultaneous estimates of the excitability and reactivity of vasopressor responses to midbrain stimulation were obtained.
Both the ascending activating system and descending vasomotor system seem to involve a muscarinic (atropine sensitive) synapse, however, evidence has been presented that, in addition to pathways involving a muscarinic synapse, these functions can be mediated over pathways devoid of muscarinic synapses.
Comparing activation patterns obtained in the presence of atropine with those obtained in the presence of pentobarbital, it has been possible to dissociate two effects of activation on spontaneous cortical potentials: (1) inhibition or depression of cortical waves, and (2) acceleration of frequency of cortical waves. Both of these effects appear to be graded. Evidence has been presented indicating that the high voltage fast activity observed after small to moderate doses of barbiturates may represent spindle activity that has been accelerated by the activating system.
Chlorpromazine and chlorpromazine sulfoxide were found to decrease the excitability of both the ascending activating system and the descending vasomotor system. The depression of excitability was better correlatedwith the adrenergic potentating property of these agents than with their adrenergic blocking activity.
Atropine, chlorpromazine and chlorpromazine sulfoxide were found to increase both threshold and reactivity of the ascending activating system.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arduini, A., and M. G. Arduini: Effect of drugs and metabolic alterations on brain stem arousal mechanism. J. Pharmacol. exp. Ther. 110, 76–85 (1954).
Bonvallet, M., P. Dell and G. Hiebel: Tonus sympathique et activité électrique corticale. Electroenceph. clin. Neurophysiol. 6, 119–144 (1954.)
Bradley, P. B.: The central action of certain drugs in relation to the reticular formation of the brain, Chap. 5, pp. 123–149 in: Reticular formation of the brain, pp. 766. Boston, Mass.: Little, Brown & Co. 1958.
—, and J. Elkes: The effects of some drugs on the electrical activity of the brain. Brain 80, 77–117 (1957).
—, and A. J. Hance: The effect of chlorpromazine and methopromazine on the electrical activity of the brain in the cat. Electroenceph. clin. Neurophysiol. 9, 191–215 (1957).
—, and B. J. Key: The effect of drugs on arousal responses produced by electrical stimulation of the reticular formation of the brain. Electroenceph. clin. Neurophysiol. 10, 97–110 (1958).
Brazier, M. A. B.: Physiological mechanisms underlying the electrical activity of the brain. J. Neurol. Neurosurg. Psychiat. 11, 118–132 (1948).
—, and J. E. Finesinger: Action of barbiturates on the cerebral cortex. Electroencephalographic studies. Arch. Neurol. Psychiat. (Chicago) 53, 51–58 (1945).
Cahen, R. L., and K. M. Tvede: Action of atropine on sympathetic ganglia. Arch. int. Pharmacodyn. 94, 248–256 (1953).
Daly, M. B., and P. G. Wright: The effect of anticholinesterases upon peripheral vascular resistance in the dog. J. Physiol. (Lond.) 133, 475–497 (1956).
DeMaar, E. W. J., W. R. Martin and K. R. Unna: Chlorpromazine II. The effects of chlorpromazine on evoked potentials in the midbrain reticular formation. J. Pharmacol. exp. Ther. 124, 77–85 (1958).
Dirnhuber, P., and H. Cullumbine: The effect of anticholinesterase agents on the rats' blood pressure. Brit J. Pharmacol. 10, 12–15 (1955).
Domino, E. F.: A pharmacological analysis of the functional relationship between the brain stem arousal and diffuse thalamic projection systems. J. Pharmacol. exp. Ther. 115, 449–463 (1955).
—, and R. F. Hudson: Observations on the pharmacological action of the isomers of atropine. J. Pharmacol. exp. Ther. 127, 305–312 (1959).
French, J. D., M. Verzeano and H. W. Magoun: A neural basis for the anesthetic state. A.M.A. Arch. Neurol. Psychiat. 69, 519–529 (1953).
Henderson, V. E.: On the sensitivity of different nerve endings to atropine. J. Pharmacol. exp. Ther. 21, 99–102 (1923).
Kabat, H., H. W. Magoun and S. W. Ranson: Electrical stimulation of points in the forebrain and midbrain. Arch. Neurol. Psychiat. (Chicago) 34, 931–955 (1935).
Killam, K. F., and E. K. Killam: Drug action on pathways involving the reticular formation, Chap. 4, pp. 111–122 in: Reticular formation of the brain, pp. 766. Boston, Mass.: Little, Brown & Co. 1958.
King, E. E.: Differential action of anesthetics and interneuron depressants upon EEG and recruitment responses. J. Pharmacol. exp. Ther. 116, 404–417 (1956).
Lindgren, P.: The mesencephalon and the vasomotor system. Acta physiol. scand. 35, Suppl. 121, 1–189 (1955).
Longo, V. G.: Effects of scopolamine and atropine on electroencephalographic and behavioral reactions due to hypothalamic stimulation. J. Pharmacol. exp. Ther. 116, 198–208 (1956).
Marrazzi, A.: The action of parasympathomimetic drugs on sympathetic ganglia. J. Pharmacol. exp. Ther. 65, 18–35 (1939).
Martin, W. R., D. H. Abdulian, K. R. Unna and H. Busch: A study of the peripheral and central actions of dibromopyruvic acid. J. Pharmacol. exp. Ther. 124, 64–72 (1958).
-, J. L. Riehl and K. R. Unna: Chlorpromazine III. The effects of chlorpromazine and chlorpromazine sulfoxide on vascular responses to l-epinephrine and levarterenol. J. Pharmacol. exp. Ther. 1960 (in press).
Moran, N. C., and W. M. Butler: The pharmacological properties of chlorpromazine sulfoxide, a major metabolite of chlorpromazine. A comparison with chlorpromazine. J. Pharmacol. exp. Ther. 118, 328–337 (1956).
Moruzzi, G., and H. W. Magoun: Brain stem reticular formation and activation of EEG. Electroenceph. clin. Neurophysiol. 1, 455–473 (1949).
Purpura, D. P.: Observations on the cortical mechanism of reticulocortical activation accompanying behavioral arousal. Science 123, 804 (1956).
Riehl, J. L., and K. R. Unna: Effects of muscarine and arecoline on the central nervous system. Biol. Psychiat.; S. Wortis ed. (in press).
Rinaldi, F., and H. E. Himwich: Alerting responses and actions of atropine and cholinergic drugs. A.M.A. Arch. Neurol. Psychiat. 73, 387–395 (1955).
Rothballer, A. B.: The effects of catecholamines on the central nervous system. Pharmacol. Rev. 11, 494–547 (1959).
Scheibel, M. E., and A. B. Scheibel: Structural substrates for integrative patterns in brain stem reticular core, Chap. 2, pp. 31–55 in: Reticular formation of the brain, pp. 766. Boston, Mass.: Little, Brown & Co. 1958.
Varagić, V.: The action of eserine on the blood pressure of the rat. Brit. J. Pharmacol. 10, 349–353 (1955).
Whitlock, D. G., A. Arduini and G. Moruzzi: Microelectrode analysis of pyramidal system during transition from sleep to wakefulness. J. Neurophysiol. 16, 414–429 (1953).
Wikler, A.: Pharmacological dissociation of behaviour and EEG “sleep patterns” in dogs: morphine, N-allylnormorphine and atropine. Proc. Soc. exp. Biol. (N.Y.) 79, 261–265 (1952).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Martin, W.R., Eades, C.G. A comparative study of the effect of drugs on activating and vasomotor responses evoked by midbrain stimulation: Atropine, pentobarbital, chlorpromazine and chlorpromazine sulfoxide. Psychopharmacologia 1, 303–335 (1960). https://doi.org/10.1007/BF00404228
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00404228