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The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress*
0013-7227/99/$03.00/0 Vol. 140, No. 1 Endocrinology Printed in U.S.A. Copyright © 1999 by The Endocrine Society The Impact of the Nonpeptide Corticotropin-Releasing Hormone Antagonist Antalarmin on Behavioral and Endocrine Responses to Stress* TERRENCE DEAK, KIEN T. NGUYEN, ANDREA L. EHRLICH, LINDA R. WATKINS, ROBERT L. SPENCER, STEVEN F. MAIER, JULIO LICINIO, MA-LI WONG, GEORGE P. CHROUSOS, ELIZABETH WEBSTER, AND PHILIP W. GOLD Department of Psychology (T.D., K.T.N., A.L.E., L.R.W., R.L.S., S.F.M.), University of Colorado, Boulder, Colorado 80309-0345; Clinical Neuroendocrinology Branch (J.L., M.-L.W., P.W.G.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1284; and Developmental Neuroendocrinology Branch (G.P.C., E.W.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1284 ABSTRACT Furthermore, because rats previously exposed to inescapable shock The nonpeptide CRH antagonist antalarmin has been shown to (IS; 100 shocks, 1.6 mA, 5 sec each), demonstrate enhanced fear block both behavioral and endocrine responses to CRH. However, it’s conditioning, we investigated whether this effect would be blocked by potential activity in blunting behavioral and endocrine sequelae of antalarmin. Antalarmin (20 mg/kgz2 ml ip) impaired both the induc- stressor exposure has not been assessed. Because antagonism of cen- tion and expression of conditioned fear. In addition, antalarmin tral CRH by a-helical CRH attenuates conditioned fear responses, we blocked the enhancement of fear conditioning produced by prior ex- sought to test antalarmin in this regard. -
Adverse Effects of Stress on Drug Addiction
Making a bad thing worse: adverse effects of stress on drug addiction Jessica N. Cleck, Julie A. Blendy J Clin Invest. 2008;118(2):454-461. https://doi.org/10.1172/JCI33946. Review Series Sustained exposure to various psychological stressors can exacerbate neuropsychiatric disorders, including drug addiction. Addiction is a chronic brain disease in which individuals cannot control their need for drugs, despite negative health and social consequences. The brains of addicted individuals are altered and respond very differently to stress than those of individuals who are not addicted. In this Review, we highlight some of the common effects of stress and drugs of abuse throughout the addiction cycle. We also discuss both animal and human studies that suggest treating the stress- related aspects of drug addiction is likely to be an important contributing factor to a long-lasting recovery from this disorder. Find the latest version: https://jci.me/33946/pdf Review series Making a bad thing worse: adverse effects of stress on drug addiction Jessica N. Cleck and Julie A. Blendy Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. Sustained exposure to various psychological stressors can exacerbate neuropsychiatric disorders, including drug addiction. Addiction is a chronic brain disease in which individuals cannot control their need for drugs, despite negative health and social consequences. The brains of addicted individuals are altered and respond very differently to stress than those of individuals who are not addicted. In this Review, we highlight some of the common effects of stress and drugs of abuse throughout the addiction cycle. -
WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/072852 Al 21 May 2015 (21.05.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 36/84 (2006.01) A61K 31/5513 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/045 (2006.01) A61P 31/22 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/522 (2006.01) A61K 45/06 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/NL20 14/050780 KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (22) International Filing Date: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 13 November 2014 (13.1 1.2014) PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, 61/903,430 13 November 2013 (13. 11.2013) US GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, (71) Applicant: RJG DEVELOPMENTS B.V. -
Neuropeptides: Implications for Alcoholism
Journal of Neurochemistry, 2004, 89, 273–285 doi:10.1111/j.1471-4159.2004.02394.x REVIEW Neuropeptides: implications for alcoholism Michael S. Cowen*, , Feng Chen*, and Andrew J. Lawrence*, *The Howard Florey Institute, University of Melbourne, VIC 3010, Australia Department of Pharmacology, Monash University, VIC 3800 Australia Abstract (CRF), urocortin I and neuropeptide Y (NPY) in deleterious The role of neuromodulatory peptides in the aetiology of and excessive alcohol consumption, focussing on specific alcoholism has been relatively under-explored; however, the brain regions, in particular the central nucleus of the development of selective ligands for neuropeptide receptors, amygdala, that appear to be implicated in the pathophysi- the characterization and cloning of receptors, and the ology of alcoholism. The review also outlines potential development of transgenic mouse models have greatly directions for further research to clarify neuropeptide facilitated this analysis. The present review considers the involvement in neuromodulation within discrete brain nuclei most recent preclinical evidence obtained from animal pertinent to behavioural patterns. models for the role of two of the opioid peptides, namely J. Neurochem. (2004) 89, 273–285. b-endorphin and enkephalin; corticotropin-releasing factor Alcohol causes as much, if not more death and disabilityas analysis. However, drugs that interact with neuropeptide measles, malaria, tobacco or illegal drugs (World Health systems have great potential in the pharmacotherapy of Organization, 2001) . In economic terms, alcohol abuse has alcoholism: witness the widespread (although somewhat less been estimated at US$167 billion per year; however, ‘in than satisfactory) use of the opioid antagonist naltrexone in human terms, the costs are incalculable’ (National Institute the treatment of alcoholism (O’Malley et al. -