Neuroscience of Addiction

The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A 'self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3-6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable?

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Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

Conditioned taste aversion induced by self-administered drugs: Paradox revisited

If the entire materia medica at our disposal were limited to the choice and use of only one drug, I am sure that a great many, if not the majority, of us would choose opium ([Macht, 1915][1]).

### A. Early History

Opium is the dried milky juice of the unripe seed capsule of the poppy, the Papaver

Opioids, Reward and Addiction: An Encounter of Biology, Psychology, and Medicine

Conditioning factors in opiate addiction and relapse

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.

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

Sulfacetamide, methenamine, and mandelic acid were studied in an effort to determine which drug or combination of drugs is the most useful in the treatment of urinary tract disease. Utilizing a described method of analysis, results are reported of attempts made to produce resistant strains of organisms to the three drugs and four combinations of them. Finding the combination of all three drugs to be most useful, an excretion study was made using human subjects.

Bacterial Resistance Studies Involving Several DrugsUseful in the Treatment of Urinary Tract Disease

Six new basic derivatives of ethyl diphenyl- acetate have been subjected to a pharmaco-logical investigation. The results of antihis- taminic, antispasmodic, local anesthetic, vasodepressor, analgetic, irritant and toxicity tests are presented.

A pharmacological study of certain basic derivatives of ethyl diphenylacetate.

Phenyl alpha‐naphthyl ketimine hydrochloride has been prepared and studied for anticonvulsant and certain other pharmacological properties Definite anticonvulsant activity was shown against both Metrazol® and electric shock‐induced convulsions A positive local anesthetic, hypotensive and antipyretic effect was observed but analgesic, autonomic, and irritant activities were essentially negative Symptoms of toxicity did not occur with either single doses or with prolonged administration

Cecil P. Headlee

Papers

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

Bacterial Resistance Studies Involving Several DrugsUseful in the Treatment of Urinary Tract Disease

A pharmacological study of certain basic derivatives of ethyl diphenylacetate.

Some pharmacological properties of phenyl alpha-naphthyl ketimine.