Drug effects on behavior maintained by food, electric-shock presentation and stimulus-shock termination

Although early experiments did not find differences in drug effects depending on the type of event, more recent studies have reported several instances in which the maintaining event appeared to influence the effects of several drugs on behavior. For example, morphine, methadone, and the narcotic antagonists naloxone and nalorphine decreased responding maintained under 5-minute fixed-interval food-presentation schedules at doses that increased responding comparably maintained by the presentation of an electric shock (). Under similar schedule conditions, both amphetamine () and cocaine () increased responding maintained by these two events. However, appropriate doses of pentobarbital, ethanol, and chlordiazepoxide increased responding maintained by food, while only decreasing responding under shock-presentation schedules (). These findings suggested that there were several conditions under which certain drugs appeared to affect similar performances maintained under comparable schedules in an event-dependent manner. Further, as shown in Figure Effects of chlordiazepoxide on different control rates of responding under S-minute fixed-interval schedules of food or shock presentation. The event pen was defected downward Read more […]

Internal Stimulus Control and Subjective Effects of Drugs

For many years psychotropic drugs have been characterized and classified using methods designed to measure their subjective effects in humans (). This research approach has two principal purposes: 1) to investigate the efficacy of a drug in attenuating unwanted subjective states in patients (e.g., pain, anxiety, depression), 2) to investigate the abuse potential of new drugs by comparing their subjective effects in experienced drug abusers to those produced by known drugs of abuse. In regard to the latter, such methods have been used to determine whether there are any common subjective states produced by all drugs of abuse (e.g., euphoria). Systematic studies of subjective methods for drug classification have been conducted at the Addiction Research Center (ARC) in Lexington, Kentucky, now part of the National Institute on Drug Abuse. A major mission of the ARC has been to evaluate new analgesic compounds to determine whether they produced morphine-like effects. The subjective effects of morphine and related compounds were an important aspect of this evaluation. The research demonstrated that morphine and related narcotic analgesics produced a unique spectrum of subjective effects that can be reliably discriminated Read more […]

History of Drug Exposure as a Determinant of Drug Self-Administration

The purpose of this paper is to review how a drug’s effectiveness in initiating and maintaining self-administration can be influenced by a subject’s past experience with drugs. Drug self-administration by humans and laboratory animals is considered an instance of operant behavior (), controlled by the subject’s genetic constitution, past history, and the current circumstances of drug availability (of Skinner, 1938). The influence of history of drug exposure on current drug-maintained behavior may be controlled, in turn, by the particular drugs and doses employed and the conditions under which the drug is administered. This discussion will focus on the ways in which a history of drug exposure can control later drug self-administration in laboratory animals. Effects of history of drug exposure on initiation of drug self-administration In order to study drug self-administration by laboratory animals, an experimenter must set up a situation in which subjects are exposed to some contingency between the occurrence of a specific response and delivery of a particular drug. For many drugs, no explicit behavioral or pharmacologioal history is necessary for the drug to maintain behavior. In one initial study, for example, Read more […]

Behavioral Pharmacology of Narcotic Antagonists

Narcotic antagonists are currently the major pharmacological alternative to methadone for the long-term treatment of narcotic addiction. The clinical utility of antagonist treatment is undergoing continuing evaluation (). Within the last five years, there have been several comprehensive reviews of research on narcotic antagonist drugs (). This review will focus upon some recent behavioral studies of narcotic antagonist drugs in man and in animals. It is now apparent that antagonist drugs may have a number of complex behavioral effects, in addition to antagonism of the pharmacological effects of opiate drugs (). Recent explorations of the aversive properties of some antagonists () have been complemented by studies of the positive reinforcing qualities of antagonist drugs. The finding that opiate dependent monkeys will work to produce an infusion of a narcotic antagonist under certain conditions () suggests the complexity of the process of drug-related reinforcement (). Narcotic agonists and antagonists each may maintain behavior that leads to their administration. Of the several compounds which have narcotic antagonist properties), only two appear to be relatively “pure” antagonists with minimal agonistic activity. Read more […]

Effects of antagonists of opiate self-administration

Clinical Studies Since narcotic antagonists can block the effects of opiates, proponents of narcotic antagonist maintenance for the treatment of heroin addiction argue that pharmacological blockade will eventually eliminate opiate self-administration (). However, recent studies of the efficacy of naltrexone maintenance in modulating heroin self-administration on a clinical research ward have shown that some addicts may continue to sample heroin during antagonist blockade (). The frequency of heroin self-administration during antagonist blockade was influenced by a number of factors, including whether or not the heroin addict was told that he was given naltrexone. When subjects were not told who was receiving naltrexone and who was receiving naltrexone placebo, seven of the nine subjects maintained on naltrexone blockade (75 mg/day PO) sampled heroin an average of 13 times (range: 2-46) over a ten-day period of heroin availability. Assessments of temperature, blood pressure, pulse, respiration and pupil diameter revealed no physiological effect of heroin during naltrexone blockade. Although all subjects took less heroin during naltrexone blockade than under unblocked conditions (X occasions = 55.07; range: 32-78), the Read more […]

Antagonist self-administration

Primate Studies The behavioral effects of narcotic antagonists are usually concordant with expected predictions of what the effects of these agents should be. What is more intriguing and perplexing are the recent findings that, under certain conditions, opiate dependent monkeys will work to produce an infusion of a narcotic antagonist (). In 1972, Goldberg, Hoffmeister, and Schlichting () reviewed their behavioral studies of the effects of morphine antagonist administration to morphine dependent monkeys. When either saline or nalorphine was substituted for morphine during a seven and one-half hour session, it was found that responding which was followed by nalorphine injections decreased less rapidly than responding followed by saline injections. In fact, nalorphine maintained responding occurred at a higher rate than either saline maintained responding or morphine maintained responding (). These data indicate that response produced nalorphine injections (100 mcg/kg/inj) can maintain responding when monkeys are physiologically dependent on morphine. In 1975, Woods, Downs, and Carney () reported that morphine dependent monkeys, trained to avoid infusion of naloxone, will, under certain schedule conditions, work Read more […]

Multimodality Treatment of Narcotic Addiction: Pharmacologic Therapies

Narcotic substitution The single therapy that has had the greatest impact on narcotic addiction appears to be methadone maintenance. Unlike drug-free approaches, it is acceptable to a large number of addicts (). It is medically safe, has minimal side effects and no toxicity when given to tolerant individuals, even for long periods of time (). Though the results of methadone treatment vary among programs, there is strong evidence that it provides a way to control narcotic addiction. Most patients who remain in methadone treatment have a marked decrease in heroin use, an increase in employment rates, and demonstrate improved personal adjustment (). At present there are approximately 80,000 people being treated with methadone in the United States (), but despite methadone’s wide applicability and effectiveness, it leaves much to be desired. It has been controversial since the beginning, and many aspects of methadone programs have been criticized (). One problem has been an inability to demonstrate that methadone treatment increases the long term cure rate for addiction. This is a disappointment, as many had hoped that the social rehabilitation obtained via methadone maintenance would lay the groundwork for successful Read more […]

Benzodiazepine Dependence: Animal Studies

Animal models are available for the production of both psychological and physical dependence. The most important animal model for the study of psychological dependence is the operant model using an intravenous self-administration technique originally used for opiate studies (see for example references-) . The animal is trained to self-administer the drug solution through an indwelling cannula by pressing a bar which activates the injection pump. The literature, particularly that relating to opiates has been extensively reviewed and is beyond the scope of this paper. These studies have shown that different groups of drugs have different levels as operant reinforcers. Thus opiates, amphetamines and cocaine are highly potent, ethanol and barbiturates moderately so and mescaline and phenothiazines relatively ineffective. Not all animals of the same species respond to reinforcement in the same way but some develop drug intake patterns which, like those of dependent humans, lead to physical illness and gross withdrawal reactions. In such experiments benzodiazepines have shown negligible evidence of dependence production. Thus Findley, Robinson and Peregrino studied the effect of intravenous administration of chlordiazepoxide Read more […]