This chapter attempts to answer the following linked questions: 

1

What is the simplest adequate description of the effects of the “minor tranquilizers” on “emotional behavior” (terms I shall define below)?




2

What underlying psychological processes are altered by these drugs to produce these behavioral effects, and in what way are they altered?




3

On what brain structures or systems do these drugs act to produce these behavioral effects?

Drug Effects on Fear and Frustration: Possible Limbic Site of Action of Minor Tranquilizers

The sections in this article are:


1
Sleep-Wakefulness States
1.1
Identification and Organization

1.2
Mechanisms and Functions




2
Central Neuronal Sleep-Respiratory Interactions

3
Respiratory Muscle Function
3.1
General Concepts

3.2
Diaphragm and Intercostal Muscles

3.3
Upper Airway Muscles




4
Ventilation and Gas Exchange
4.1
NREM Sleep

4.2
REM Sleep




5
Pattern of Breathing
5.1
NREM Sleep

5.2
REM Sleep




6
Ventilatory Responses to Respiratory Stimuli
6.1
Response to CO2

6.2
Response to Hypoxia

6.3
Response to Upper Airway Stimulation

6.4
Response to Bronchopulmonary Stimulation

6.5
Response to Chest Wall Stimulation

6.6
Response to Thermal Stimuli




7
Arousal Responses to Respiratory Stimuli
7.1
Arousal Thresholds

7.2
Mechanisms of Arousal

7.3
Physiological Importance

Control of breathing during sleep

General Pharmacology and Neuropharmacology of Benzodiazepine Derivatives

The current era of research into the physiology of sleep began in 1953 when Aserinsky and Kleitman (2) first described REMl sleep and its association with a characteristic EEG pattern, dreaming, and changes in autonomic nervous system activity including respiration. This important discovery demonstrated conclusively that the traditional view of sleep as a homoge­ neous state was incorrect, and indicated that preexisting observations or theories regarding sleep had to be reexamined or reinterpreted taking the stage of sleep into consideration. Accordingly much of the research in sleep physiology during the past twenty years has been directed towards a defini­ tion of the physiological differences between REM and NREM sleep and towards elucidation of the specific mechanisms and purposes that underlie the different sleep stages. In recent years these same goals have been applied increasingly to the study of respiration during sleep. To the extent that the fundamental purposes and mechanisms of sleep itself remain uncertain, so too are the purposes and mechanisms of the respiratory adaptations to sleep. Nevertheless the changes in respiration that occur in the different stages of sleep have now been studied extensively, at least in purely descrip­ tive terms. In addition, attempts have been made, although fewer in num-

Respiratory Adaptations in Sleep

Reaction time (RT), a behavioral measure of arousal, was used to examine standard criteria (Rechtschaffen & Kales, 1968) for assessing sleep onset (SO) and the sensitivity of changes in respiratory patterns at SO. Following 24 hrs without sleep, RT, respiratory, and EEG measures were used to study SO in 12 subjects. Sleep deprivation (SD) permitted multiple examinations of SO in 2 daytime testing periods. Strong relationships between RT and EEG-based measures of SO serve to confirm the distinction between wakefulness and stage 1 sleep, and moderate to weak correlations between RT and respiratory indices describe the usefulness of the latter.



Behavioral, respiratory and EEG assessments of the shift from wakefulness to sleep were observed to be orderly and rapid in these SD volunteers, suggesting that the detection of SO could be sharpened by adding behavioral and respiratory measures to the usual EEG criteria. The close temporal correspondence among these changes has interesting implications for sleep/waking mechanisms.

The detection of sleep onset: behavioral and physiological convergence.

Antihypertensive Agents II: Synthesis and Hypotensive Activity of Certain 1,4,5-Trisubstituted Pyrazoles

Synthesis of 5h-dibenzo(a,d)cycloheptene derivatives with diverse biological activities

1-(5-Methyl-1-phenyl-4-pyrazolyl)-3-[4-(o-tolyl)-piperazinyl]-1-propanone (I; CIBA 1002-Go), senkt an normotonischen und hypertonischen Tieren den Blutdruck. Die Drucksenkung kann auf eine periphere Vasodilatation und eine Hemmung hypothalamischer oder medullarer Vasomotorenzentren bezogen werden. Ausserdem wirkt CIBA 1002-Go adrenolytisch.

1-(5-Methyl-1-phenyl-4-pyrazolyl)-3-[4-(o-tolyl) -piperazinyl]-1-propanone, a new synthetic antihypertensive agent.

EEG patterns in relation to respiratory rate and body movement in Macaca mulatta

The immediate and persistent effects of single oral doses of sodium pentobarbital 20 mg/kg, nitrazepam 25 mg/kg and imipramine 25 mg/kg, were compared on behavioural patterns as well as on quantitative aspects of diurnal EEG patterns in rhesus monkeys. Consecutive pre-drug EEG recordings on agar treated monkeys, showed no significant variations in day to day EEG levels of wakefulness, drowsiness, sleep and the REM state. Both the sedative-hypnotic agents, sodium pentobarbital and nitrazepam, significantly reduced wakefulness and the REM state and increased slow wave sleep. They reduced the latency to onset of slow wave sleep but significantly increased the latency to onset of the REM state. The antidepressant agent imipramine, did not influence any of the EEG parameters to a significant extent. Significantly enhanced REM levels persisted during the 7-day post-drug period after cessation of medication of all three psychoactive agents. The effect on the macaque EEG of an increase in slow wave sleep with concomitant decreased levels of wakefulness and REM with respect to baseline levels, provides a quantitative basis for comparing sedative-hypnotic agents in monkeys. Residual drug-induced EEG changes, reflected by enhanced REM levels, may prove a sensitive indicator of persistent drug effects in subhuman primates.

R. S. Grewal

Papers

Antihypertensive Agents II: Synthesis and Hypotensive Activity of Certain 1,4,5-Trisubstituted Pyrazoles

Synthesis of 5h-dibenzo(a,d)cycloheptene derivatives with diverse biological activities

1-(5-Methyl-1-phenyl-4-pyrazolyl)-3-[4-(o-tolyl) -piperazinyl]-1-propanone, a new synthetic antihypertensive agent.

EEG patterns in relation to respiratory rate and body movement in Macaca mulatta

Persistent electroencephalographic changes in rhesus monkeys after single doses of pentobarbital, nitrazepam and imipramine