Cardiovascular responses to acetylcholine: Effects of pentobarbital and autonomic blocking agents

The effect of acetylcholine chloride (ACh) on heart rate (HR) and blood pressure (BP) was studied in four dogs, awake and under anesthesia by means of pentobarbital sodium. In the awake dog, ACh caused a triphasic change in HR—a rise, fall and secondary rise. The BP showed an initial gradual fall followed by a secondary precipitous fall coinciding with the fall in HR, and then return to base line. Anesthesia accentuated the precipitous fall in HR due to ACh, and narrowed the pulse pressure during the initial fall in BP due to ACh. The effects of atropine sulphate, propranolol and d-tubacurarine on the above were studied, indicating the roles of the sympathetic and parasympathetic systems in mediating the HR and BP reactions to ACh in the awake state and under pentobarbital sodium anesthesia.     

Notes on Pavlov written while I was in Russia (1922–1927)

Editors Note—Shortly before Dr. Gantt died, he gave me the following notes that he wrote on Pavlov with the suggestion that I might edit and publish them at some time. Instead of editing them, I think these notes as they are are touching and close to both Gantt and Pavlov. They are reproduced here with only very minor, typographical corrections.—FJM     

Clamped Corticosterone (B) Reveals the Effect of Endogenous B on Both Facilitated Responsivity to Acute Restraint and Metabolic Responses to Chronic Stress

To determine the effects of both corticosterone (B) and chronic stressors on acute ACTH responses to restraint, young male rats were exposed to streptozotocin-induced diabetes, cold (5-7 degreesC) or intracerebroventricular (icv) neuropeptide Y (NPY) for 5 d and then exposed to restraint within 2 h after lights on. Two groups of rats were studied: intact and adrenalectomized replaced with B pellets that maintained plasma B in the normal mean 24-h range of intact rats. In addition to ACTH and B responses to restraint on d 5, body weight, food intake, fat depots, glucose and other hormones were measured to determine the role of stress-induced elevations in B on energy balance. ACTH responses to restraint were normal in intact rats subjected to diabetes or cold. By contrast, there was no ACTH or B response to restraint in NPY-infused intact rats. All 3 groups of chronically stimulated adrenalectomized rats with clamped B had facilitated ACTH responses to restraint compared to their treatment controls. Overall food intake increased in all groups of stressed rats; however, augmented intake occurred only during the light in intact rats and equally in the light and dark in B-clamped rats. White adipose depot weights were decreased by both diabetes and cold and increased by NPY in intact rats; the decreases with cold and increases with NPY were both blunted and changes in fat stores were not significant in adrenalectomized, B-clamped rats. We conclude that: 1. diabetes- and cold-induced facilitation of restraint-induced afferent input to hypothalamic control of the hypothalamo-pituitary-adrenal (HPA) axis is opposed in intact rats by the elevated feedback signal of B secretion; 2. NPY does not induce facilitation of afferent stress pathways; 3. chronic stimulation of the HPA axis induces acute hyperresponsiveness of hypothalamic neurons to restraint provided that the afferent input of this acute stimulus is not prevented by B feedback; 4. stimulus-induced elevations in B secretion result in day-time feeding; 5. insensitivity of both caloric efficiency and white fat stores to chronic stress in adrenalectomized, B-clamped rats results from loss of normally variable B levels.     

Pavlovian conditioning of drug reactions: Some implications for problems of drug addiction

This paper reviews the classical conditioning of drug reactions, with special emphasis on the relationship of this phenomenon to drug addiction. Several aspects of drug addiction such as drug craving, high relapse tendencies, and the recurrence of withdrawal symptoms are reviewed and interpreted in light of classical conditioning theory and data. A theory is proposed that attempts to account for various aspects of the addictive process. The implications and empirical methods for testing this theory are outlined.     

Psychopharmacology and conditional reflexes

Drugs may be used in several ways to investigate their role in behavior. (1) The placebo effect is usually connected with the relation of the person to the drug. (2) Using the drug as an unconditional stimulus, its action may help to analyze the role of peripheral vs. central stimuli in the formation of conditional reflexes; our work has shown that the effect of drugs which act solely at the peripheral nerve endings without the involvement of the central nervous system cannot become conditioned. (3) The action of drugs on the conditional reflex (CR) compared with their action on the unconditional reflex (UR) explains some of their behavioral effects. (4) Schizokinesis is often prominent in the action of drugs. Although a drug may increase the level of the heart rate, for example, it can, on the other hand, diminish the reactivity shown in the CR. Meprobamate and mescaline affect differently the cardiac and the motor components of the CR, illustrating a schizokinesis. (5) The type of individual is an important factor in the action of drugs; the same drug may have opposite effects on different individuals. This leads to the conclusion that a drug should fit the individual as well as the disease. (6) Autokinesis is often seen in drug action. Therefore a single dose of some drugs, such as acetylcholine, epinephrine or LSD, may permanently change the relationships between excitation and inhibition, in the direction of improvement or deterioration (positive or negative autokinesis).