Neuroscience of Addiction

A method has been developed which permits monkeys to self-administer drug solutions, at will, through indwelling intravenous catheters Psychological dependence on the effects of a drug occurs when a naive monkey voluntarily initiates and maintains self-administration of the drug If, in addition to psychological dependence, the drug also produces psychotoxicity, either directly or upon abrupt withdrawal, it has a potential abuse liability In the present study monkeys developed psychological dependence on morphine, codeine, cocaine, d-amphetamine, pentobarbital, ethanol, and caffeine All of these drugs except caffeine produced psychotoxicity Monkeys did not develop psychological dependence on nalorphine, morphine-nalorphine mixtures, chlorpromazine, mescaline or physiological saline

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Self-administration of psychoactive substances by the monkey.

An operant behavioral study on morphine addiction utilized a self-injection technique for giving intravenous injections to relatively unrestrained rats. The rate of self-injection varied inversely with the dose. Morphine was a reinforcer that produced almost immediate satiation.

https://science.sciencemag.org/content/sci/138/3537/143.full.pdf

Experimental Morphine Addiction: Method for Automatic Intravenous Injections in Unrestrained Rats

Though usually initiated through social reinforcement, self-administration of psychoactive drugs (SAPD) is soon reinforced pharmacologically through suppression (by each successive dose) of a homeostatic need generated by successive central counteradaptive changes (CCCs) that develop unconditionally in response to the initial (receptor site) actions of such drugs and their "reflex" consequences (signs of drug effects). Temporal contiguity between pharmacological reinforcement and recurring exteroceptive and interoceptive stimuli (CCs) results in increasing probability of occurrence of both CCCs and SAPD in the presence of the CSs (appetitive conditioning), even long after detoxification (DTX). To prevent relapse, both conditioned CCCs (conditioned abstinence, CA) and conditioned SAPD should be actively extinguished after DTX by elicitation of CA and programmed SAPD under conditions preventing pharmacological reinforcement. Associated psychopathologies and previous state-dependent learning may pose problems in rehabilitation.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=psych&articleId=490887&pdfFileName=archpsyc_28_5_001.pdf

Dynamics of drug dependence. Implications of a conditioning theory for research and treatment.

The effects of large doses of morphine in nontolerant and tolerant rats as well as the effects of abruptly withdrawing morphine in rats experimentally addicted to large doses of morphine have been studied on body weight, temperature, metabolic rate, respiratory rate, water consumption and various forms of motor activity and behavior. In confirmation of many early reports, tolerance develops to certain depressant actions of large doses of morphine and the effects of morphine in the tolerant rat are primarily excitatory, consisting of an increase in body temperature, metabolic rate and motor activity. The abstinence syndrome of rats addicted to large doses of morphine seems to have two phases: (1) An early phase, which has been called “primary abstinence” consists of weight loss, an increased number of “wet dog” shakes, increased activity, and a fall in body temperature and metabolic rate. The primary abstinence syndrome becomes clearly manifest within 8 to 16 hours following the last dose of morphine and persists for approximately 72 hours. (2) The secondary abstinence syndrome emerges thereafter and consists of a rapid gain in body weight, elevated body temperature and metabolic rate and an increase in water consumption. The secondary abstinence syndrome is protracted and small differences have been seen between addicted and control animals as long as four to six months after withdrawal of morphine.

Tolerance to and physical dependence on morphine in rats.

Withdrawal has been shown to be a motivating state which may be used to promote learning a new action, if this new action reduces the level of withdrawal. The withdrawal syndrome may be considered a noxious stimulus to which the animal learns an action which reduces the severity of the noxious stimulus. This form of learning is called escape training and is a form of conditioned response. Relapse by animals was demonstrated and the importance of the confirmation of the escape training hypothesis was discussed.

Drug Addiction. I. Addiction by Escape Training

A new procedure for the laboratory determination of drug addiction has been devised and subjected to a preliminary trial using rats as experimental subjects. Automatic equipment has been constructed and utilized to produce permanent records indicating the influence of morphine, codeine, glucose, saline, and insulin administration to pretreated and deprived animals. Preliminary data indicate the method to be worthy of further study.

Harold W. Coppock

Papers

Drug Addiction. I. Addiction by Escape Training

Apparatus and technique involved in a laboratory method of detecting the addictiveness of drugs