Activation of the hypothalamic-pituitary-adrenal axis by addictive drugs: different pathways, common outcome.
Addictive drugs (opiates, ethanol, cannabinoids (CBs), nicotine, cocaine, amphetamines) induce activation of the hypothalamic-pituitary-adrenal (HPA) axis, with the subsequent release of adrenocorticotropic hormone and glucocorticoids. The sequence of events leading to HPA activation appears to start within the brain, suggesting that activation is not secondary to peripheral homeostatic alterations. The precise neurochemical mechanisms and brain pathways involved are markedly dependent on the particular drug, although it is assumed that information eventually converges into the hypothalamic paraventricular nucleus (PVN). Whereas some drugs may act on the hypothalamus or directly within PVN neurons (i.e. ethanol), others exert their primary action outside the PVN (i.e. CBs, nicotine, cocaine). Corticotropin-releasing hormone (CRH) has a critical role in most cases, but the changes in c-fos and CRH gene expression in the PVN also reveal differences among drugs. More studies are needed to understand how addictive drugs act on this important neuroendocrine system and their functional consequences.
Institute of Neurosciences and Animal Physiology Unit (Department of Cellular Biology, Physiology and Immunology), Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain. antonio.armario@uab.es
Antonio
A
Armario
D000661:Amphetamine / Q000378:metabolism / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000378:metabolism / Q000494:pharmacology*; D003042:Cocaine / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism*; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D002186:Cannabinoids; D002491:Central Nervous System Agents; D000431:Ethanol; D009538:Nicotine; D000661:Amphetamine; D003042:Cocaine