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HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY II 



(109). The reticular formation is known to be a multi- 

 neuronal system as compared to the paucisynaplic 

 direct sensory pathways, therefore, the former region 

 would appear to be far more susceptible to these 

 drugs than the latter. 



The selective susceptibility to anesthesia of such 

 polysynaptic systems as the RAS has been empha- 

 sized in the past (12, 80, 84). It was demonstrated, 

 for example, that potentials evoked in the reticular 

 formation were completely blocked following the 

 administration of ether, barbital and other central 

 nervous system depressants. By contrast, responses 

 to the same stimuli persisted or were even enhanced 

 in the medial lemniscus and postcentral gyrus follow- 

 ing anesthesia (84), even though their latency was 

 slightly prolonged {31) and the recovery time to 

 paired shocks was extended ( 1 74) . 



The above evidence clearly indicates that anes- 

 thetics do not prevent impulses conducted in primary 

 systems from reaching the brain, even though such 

 cortical inputs arrive in a somewhat modified form. 

 In the case of more widely distributed cerebral po- 

 tentials, a paradox exists. Responses with moderately 

 long latencies (12 to 30 msec.) evoked in widespread 

 cortical loci from sensory nerve or reticular formation 

 stimulation are obtainable only in the unanes- 

 thetized preparation (198, 262) while the 'second- 

 ary" response of Forbes (77), also conducted pre- 

 sumably through centrally located pathways in the 

 brain stem, is enhanced by barbital anesthesia. The 

 answer may lie in Morison's suggestion (Morison, 

 R. S., personal communication) that the latter pro- 

 jections traverse an extrathalamic route while the 

 former are conducted by thalamic as well as by sub- 

 thalamic structures. 



The effects of anesthetic agents upon spontaneous 

 and driven cortical EEG rhythms are well established, 

 but interpretation of the mechanisms involved has 

 varied considerably. In general, cortical desynchrony 

 and alpha rhythms which accompany wakefulness 

 are replaced by the synchrony and spindling of 

 sleep following anesthetic administration. Moreover, 

 rapidly repetitive stimulation (e.g. 50 per sec.) of the 

 reticular formation, either directly or through excita- 

 tion of its collateral sensory input, does not result in 

 activation of the record in the anesthetized animal 

 (12, 80). In contrast, the recruiting response elicited 

 by 6 to 12 cps stimulation of the diffusely projecting 

 thalamic nuclei is enhanced by barbiturates, although 

 ether blocks this response as it does EEG activa- 

 tion (140). 



In addition to elimination of the arousal response, 



anesthetic agents seriously modify caudally-directed 

 functions of the RAS which are expressed upon motor 

 and sensory systems. Blockade of brain-stem activitv, 

 such as is known to exist in the anesthetic state, renders 

 the subject quite atonic and incapable of voluntary 

 or even reflex movement. Animals which were made 

 chronically spastic by extirpation of the cruciate 

 region relaxed under anesthesia (205), suggesting 

 that tonic facilitatory influences from the reticular 

 formation ceased with anesthesia. 



However, there are divergent effects of drugs upon 

 the reticular formation which make it necessary to 

 re-examine the thesis that desynchrony is the in- 

 evitaijle electrographic behavioral manifestation of 

 wakefulness and that synchrony and sleep always 

 occur together. Funderburk & Case (87) have shown 

 that atropinized animals appear awake and alert 

 yet exhibit a synchronized EEG and the observation 

 has been confirmed by Bradley & Elkes (30). It 

 might be proposed that atropine blocks a cholinergic 

 desynchronizing mechanism in the reticular forma- 

 tion (236) yet does not interfere with other reticular 

 phenomena related to the preservation of behavioral 

 wakefulness. By contrast, reserpine tends to induce 

 inattentiveness and drowsiness without synchronizing 

 the low voltage fast activity in the EEG (139)- 

 Mephcnesin, an interneuron blocking agent without 

 anesthetic properties, depresses the recruiting response 

 elicited by stimulation of the diffuse thalamic projec- 

 tion system but does not alter EEG arousal from the 

 mesencephalic reticular formation (140). Chlorpro- 

 mazine causes only a slight increase in stimulus 

 threshold for EEG arousal from thalamic stimulation 

 but increases by lo-fold the current required to elicit 

 behavioral arousal from the same site (139). Behavioral 

 and EEG arousal following reticular formation 

 stimulation were not critically affected by this drug. 



MOOD-ALTERING DRUGS. The esidcnce available at 

 present concerning the mode of action of the so- 

 called 'mood-altering' drugs is not only meager Ijut 

 highly confusing as well. Leake (147, 148) and otiiers 

 have called attention to the fact that all substances 

 which induce these changes in 'mood' have in common 

 an indole or indole-like linkage in their chemical 

 structure. It has been further pointed out (147) that 

 epinephrine and in particular its metabolites, such 

 as adrenochrome and 5-hydroxytrytamine (sero- 

 tonin), contain this linkage. Moreover, other sub- 

 stances such as lysergic acid-diethylamide (LSD) 

 and even the alkaloids, cocaine, atropine and mor- 

 phine have important structural similarities. All of 



