R. T. Kelleher

Second-Order Schedules of Drug Injection

Key-press responding of squirrel monkeys produced intravenous injections of cocaine under two simple types of schedule. Under a fixed ratio schedule, every 30th response produced an injection; steady responding at high rates of over one per second were maintained during each fixed-ratio component. Under a fixed-interval schedule, the first response occurring after a fixed time of 5 min produced an injection; there was a pause at the start of each interval and then progressively increasing responding until cocaine was injected at the end of the interval. Both squirrel monkeys and rhesus monkeys also were studied under second-order schedules of drug injection. Under one type of second-order schedule, studies only in squirrel monkeys, completion of each fixed-interval component produced only a 2 sec light; completion of the 10th fixed-interval component produced the brief light and an intravenous injection of cocaine. Under a second type of second-order schedule, each fixed-ratio component completed during a fixed time interval (5 or 60 min) produced only a 2-sec light; the first fixed-ratio component completed after the interval of time elapsed produced the brief light and an intravenous (squirrel monkeys) or intramuscular (rhesus monkeys) injection of cocaine. Under both types of second-order schedules, repeated sequences of responding were maintained during each session and characteristic fixed-interval or fixed-ratio patterns of responding were controlled by the brief visual stimuli.

Effects of Drugs on Schedule-Controlled Behavior and Cardiovascular Function in the Squirrel Monkey

Environmental circumstances can modulate physiological functions and alter the action of drugs. There is now much systematic information on how the behavioral effects of drugs are modified by environmental determinants of behavior. Most drugs have selective actions on behavior in different situations, and predictions about the behavioral effects of a drug require knowledge about the conditions under which the drug is acting and the determinants of behavior in that situation. In some instances the profound effects of environmental factors in modifying the actions of drugs apply to the toxic effects of drugs; for example, it is now well known that changing the environmental circumstances can markedly enhance the lethality of amphetamine (Chance, 1946, 1967; Gunn and Gurd, 1940; Hohn and Lasagna, 1960; Weiss et al., 1961.)

Pharmacological studies of behavioral influences on cardiovascular function

Squirrel monkeys, prepared with chronic arterial and venous catheters, responded (pressed a key) under fixed-ratio schedules of termination of a stimulus associated with electric shock or under fixed-ratio schedules of food presentation. Although there was no necessary correlation between schedule-controlled responding and cardiovascular changes, pronounced elevations in both heart rate and blood pressure occurred during and just after brief periods of fixed-ratio responding. These episodic increases in blood pressure and heart rate were as marked under schedules of food presentation as under schedules of stimulus-shock termination. Thus, these episodic changes appear to be more dependent upon the schedule-controlled behavior than upon the type of event maintaining the behavior. Pharmacological studies indicated that under the conditions of the behavioral experiments the squirrel monkey has a relatively high degree of cardiac sympathetic tone; however, blood pressure elevations produced by administration of 1-norepinephrine were associated with an increased parasympathetic tone and decreased heart rate. The reflex bradycardia induced by 1-norepinephrine was inhibited during periods of schedule-controlled responding, suggesting that environmental and behavioral factors can not only modulate the parameters of physiological variables but also modulate this basic cardiovascular control system.