The antiestrogenic effect of cigarette smoking in women

The goal of this article is to summarize available data examining the physiological significance of brain corticotropin-releasing factor (CRF) systems in mediating the behavioral and physiological effects of several classes of abused drugs, including opioid and psychostimulant drugs, alcohol and sedative hypnotics, nicotine, and cannabinoids. An initial discussion of CRF neurobiology is followed by consideration of the role of CRF in drug-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, the behavioral effects of drugs (e.g., locomotor activity, anxiogenic-like responses), drug self-administration, drug withdrawal, and relapse to drug-seeking. Subsequently, neurochemical changes in brain CRF in response to acute and chronic drug exposure are examined. A major conclusion derived from the data reviewed is that extrahypothalamic brain CRF systems are critically involved in behavioral and physiological manifestations of drug withdrawal and in relapse to drug-taking behavior induced by environmental stressors. On the other hand, it appears that hypothalamic CRF, via its action on the HPA axis, is involved in the reinforcing effects of cocaine and alcohol, and the locomotor activating effects of psychostimulant drugs. These preclinical data may provide a rationale for the development of CRF-based pharmacotherapies for the treatment of compulsive drug use in humans.

The Role of Corticotropin-Releasing Factor in Drug Addiction

Numerous studies dissecting the basic mechanisms that control sleep regulation have led to considerable improvement in our knowledge of sleep disorders It is now well accepted that transitions between sleep and wakefulness are regulated by complex neurobiologic mechanisms, which, ultimately, can be delineated as oscillations between two opponent processes, one promoting sleep and the other promoting wakefulness The role of several neurotransmitter or neuromodulator systems, including noradrenergic, serotonergic, cholinergic, adenosinergic, and histaminergic systems and, more recently, the hypocretin/orexin and dopamine systems, has been clearly established Amphetamine-like stimulants are known to increase wakefulness by blocking dopamine reuptake, by stimulating dopamine release, or by both mechanisms Modafinil may increase wakefulness through activation of noradrenergic and dopaminergic systems, possibly through interaction with the hypocretin/orexin system Caffeine inhibits adenosinergic receptors, which in turn can produce activation via interaction with GABAergic and dopaminergic neurotransmission Nicotine enhances acetylcholine neurotransmission in the basal forebrain and dopamine release Understanding the exact role of the hypocretin/orexin and dopamine systems in the physiology and pharmacology of sleep-wake regulation may reveal new insights into current and future wakefulness-promoting drugs

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What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications.

The hypothalamic-pituitary-adrenal (HPA) axis in habitual smokers.

Neuroendocrine actions of nicotine and of exposure to cigarette smoke: medical implications.

Nicotine was found to raise dramatically plasma corticosterone levels in a dose-dependent manner. Plasma corticosterone time course for the 100 microgram/kg dose of nicotine produced an initial increase in corticosterone elevation which did not return towards control levels until after 30 min. The 200 and 500 microgram/kg doses, however, indicated a biphasic response for nicotine-induced steroid secretion. The first steroid peak occurred 1-15 min after nicotine administration and was followed by a greater elevation at 20 min. Plasma nicotine levels did not show the same biphasic pattern. The nicotine-induced plasma steroid elevation was completely abolished by hypophysectomy, indicating that the response to nicotine must be mediated through ACTH release from the anterior pituitary. The administration of exogenous ACTH to rats pretreated with betamethasone was found to result in a biphasic plasma steroid elevation similar to that seen after injection of 200 microgram/kg nicotine. It was postulated that this may reflect a differential response of the adrenal cortex to a single ACTH outflow.

Bassett

Papers

The action of nicotine on the pituitary-adrenal cortical axis.