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Drug addiction has a great negative influence on society, both social and economic burden. It was widely thought that addicts could choose to stop using drugs if only they had some self-control and principles. Nowadays, science has changed this view, defining drug addiction as a complex brain disease that affects behavior in many ways, both biological and psychological. Currently there is no ground-breaking reliable treatment for drug addiction. For more than a decade we are researching an alternative approach for intervention with drug craving and relapse to its usage, using DHEA, a well-being and antiaging food supplement. In this chapter we navigate through the significant therapeutic effect of DHEA on the brain circuits that control addiction and on behavioral performance both in animal models and addicts. We suggest that an integrative program of add-on DHEA treatment may further enable to dynamically evaluate the progress of rehabilitation of an individual patient, in a comprehensive assessment. Such a program may boost and support the detoxification and rehabilitation process, and help patients regain a normal life in a shorter amount of time.

The current chapter describes the role of β-endorphin and its opioid receptor type delta (DOR) in cocaine reward, reinforcement, and craving, and in new studies of relapse to cocaine usage. The studies described herein employed diverse techniques, including biochemical and molecular measurements of β-endorphin and DOR in addiction-related brain sites, and behavioral measurements conducted following elimination or augmentation of β-endorphin or DOR (via knockout mice and intracerebral or systemic pharmacological manipulations). The emerging data indicate a close relationship between cocaine-related behavior and changes in β-endorphin levels and DOR in the mesolimbic reward pathway, and particularly in the nucleus accumbens. The various findings imply that manipulation of β-endorphin and DOR can provide a breakthrough in the treatment of cocaine addiction.

For decades, clinical treatment of depression has usually involved antidepressants that target noradrenergic and serotonergic neurotransmission. Over the past half century, no genuinely ground-breaking progress has been made in the pharmacological development of antidepressant drugs. Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Recent findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with mathematical analysis. In this chapter comprehensive review of data from animal models, genetics, neuroimaging and human clinical trials that strengthen the case for dopaminergic dysfunction in the pathophysiology of major depression. This chapter focuses on recent convergence of data describing the fluctuation in activity of the mesolimbic dopaminergic system, and discusses its crucial role in manifestation of depressive-like behavior. Decoding the functionality of the dopaminergic system is important to the understanding of depression and the development of future efficient antidepressant treatments.

Publisher Summary Research suggests that strychnine and glycine interact with the agonist binding site of the nicotinic acetylcholine receptor (AChR) in chromaffin cells, thus exerting a pharmacological effect that may have a modulatory role on the AChR. The chromaffin cell has been extensively studied as a cholinergic neurosecretory system, and activation of the nicotinic receptor in these cells leads to the Ca 2+ dependent exocytotic release of catecholalmines, adenosine triphosphate (ATP), chromogranins, and enkephalins. These cells possess a high-affinity [ 3 H]strychnine binding site, and glycine can evoke catecholamine release from adrenomedullary tissue in vitro and in vivo , as demonstrated by the use of microdialysis techniques. The α 3 subunit of glycine receptors (but not the α 1 , or α 2 ) is expressed in rat adrenal and may mediate this effect. Strychnine inhibits the nicotinic stimulation of catecholamine release from cultured bovine adrenal chromaffin cells in a concentration-dependent (1–100 pM) manner. At 10 pM of nicotine, the IC 50 value for strychnine is approximately 30 pM. Strychnine also inhibits the nicotine-induced membrane depolarization and increase in intracellular Ca 2+ concentration. The inhibitory action of strychnine is reversible and is selective for nicotinic stimulation, with no effect observed on secretion elicited by a high external K + concentration, histamine, or angiotensin II.