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Wednesday, 18.10.2017

Thomas A. Ban: Psychopharmacology. Baltimore: Williams and Wilkins; 1969

Leon S. Morra’s Extracts - 10
Part One, Chapter Two: Animal Pharmacology
A. Pharmacodynamics
4. Site of Action. a. Neurophysiological Correlates

            “The discovery of the functional importance of the reticular formation together with the findings by  electro-anatomical and physiological studies renewed interest in the limbic system. These developments provided additional support for Papez’s assertion that the strongly developed fiber connections between the hippocampus, mammillary bodies, anterior thalamus and cingulate gyrus suggested a ‘functional circuit largely concerned with emotion and its expression’. Further investigations, revealed that the limbic system, the reticular formation and other related structure (hypothalamus, and septal nuclei) form a complex and integrated system (with connections to the extrapyramidal system, thalamic nuclei and cerebral cortex) which is closely connected with the various aspects of psychological functioning.”

            “The action of psychopharmacological substances on the following structures have been explored (in ascending order): autonomic nervous system, spinal cord, medulla oblongata, brain stem reticular formation, hypothalamus, thalamus, septum, amygdala, hippocampus and the cerebral-cortex. Direct information on the changes in the electrical activity of these structures following psychoactive drug administration, can be obtained by implanted electrodes techniques. By this method, drug induced changes on the spontaneous electrical activity of any particular section of the brain and the electrical after-effects of direct stimulation can be studied.”

            “Autonomic nervous system responses are intimately related to “affectivity” in general and “emotions” in particular…. Sedatives, e.g., barbiturates, have an inhibiting effect on parasympathetic ganglia [whereas] stimulants, e.g., amphetamines, produce characteristic sympathotonic changes… MAOI antidepressants were recognized as central sympathotonic drugs [whereas] tricyclic antidepressants are known for their strongly parasympatholytic action.”

            “The action of psychoactive substances on the spinal cord is seen in their effects on the monosynaptic front-leg reflex (knee jerk) and the polysynaptic hind-limb reflex…. Anxiolytic benzodiazepines and propanediols have an inhibitory effect on the monosynaptic and polysynaptic reflex functions.”

            “The action of psychoactive drugs on the medullary centers in vivo has been detected primarily by their effect on the vomiting center…”

            “The complex psychological function, consciousness is related to the activity of brain stem reticular activating system... Sedative barbiturates have a particularly strong depressant effect on the brain stem reticular activating system [whereas] stimulant amphetamines lower the electroencephalographic and behavioral threshold for arousal… MAOI’s have a stimulating effect [whereas] tricyclic antidepressant drugs, an inhibitory ‘suppressant’ action first, which later is replaced by ‘chronic arousal’... It was surmised that chlorpromazine might exert its antipsychotic actions by reducing the excessive transmission of unselected sensory information (stimuli), which might explain the sleep-inducing properties of this drug, without a blockade of all sensory communications (input)……”

            “The primary function of the hypothalamus is regulatory…With the use on the Olds and Milner technique… it was revealed that self-stimulation is selectively facilitated by psychostimulants, especially by the amphetamines and to a lesser extent by cocaine…… It was also noted that tricyclic antidepressants increased self-stimulation only when electrodes were placed in the lateral hypothalamic nuclei...”

            “The effects of the psychoactive drugs on the thalamus [were studied.] Stimulants, e.g., amphetamines decrease the recruiting activity of the thalamic intralaminary system, as opposed to sedatives, e.g., barbiturates, which enhance this activity……..antipsychotics in small doses produced an enhancement of the recruiting response similar to that seen with barbiturates… Anxiolytic benzodiazepines produce a general inhibitory effect on thalamic functions…

            “In psychopharmacological studies with implanted electrode techniques, tricyclic antidepressants had a depressant effect on inhibitory septal areas… Anxiolytic drugs also shorten the duration of after-discharges from the same areas.”

            “…the amygdala has a facilitating effect on hypothalamic activity and concomitantly on emotional output. It also appears to play a role in conditioning and learning…MAOI antidepressants enhance the excitability of this structure, i.e., lower the threshold to electrical stimulation and prolong the time of after-discharges. Tricyclic antidepressants have a similar effect but to a lesser degree… Anxiolytics suppress the activity of the amygdala… the anxiolytic effect of benzodiazepines is, related to their effect on the amygdala… Antipsychotic shorten the duration of characteristic seizure-like discharges from the amygdala...”

            “…stimulant amphetamines transiently suppress the activity of the hippocampus [whereas] sedative barbiturates exert a transient excitatory effect… MAOI’s were found to have an inhibitory influence, manifested in suppressed after-discharge to direct electrical stimulation without an actual change in the threshold of stimulation, tricyclic antidepressants induced a ‘convulsant brain-wave pattern’ originating in the hippocampal region… Anxiolytics slow the spontaneous electrical activity and depress hippocampal after-discharges to direct stimulation [whereas] antipsychotic Rauwolfias induce a regular, continuous electrical activity in the hippocampus…”

            “According to the classical view, the frontal cortex is concerned with motor and social integration, the parietal lobe with sensory and spatial functions and the temporal lobe with complex sensory integration and emotions. More recently, based on Penfield and Jasper’s (1954) work, it has been suggested that the temporal lobes are also involved in the interpretation of experience and possibly, in the ‘laying down’ of permanent memory stores.” 

            “Differential effects of psychoactive drugs on the cerebral cortex were demonstrated by surface electroencephalographic recording. Stimulants in general increase the frequency and decrease the voltage… Antidepressants do not show any uniform action… Anxiolytics, produce a shift toward fast activity and synchronization, while the effect of antipsychotic is characterized by protraction (slowing) of the basal rhythm, increased delta activity and induction of spontaneous seizure discharges…”

 

Leon S. Morra

April 20, 2017