S G Lindell1,2, M L Schwandt2, S J Suomi3, K C Rice4, M Heilig2,5, C S Barr1,2. 1. Laboratory of Comparative Behavioral Genomics, NIH/NIAAA/LNG, USA. 2. Laboratory of Clinical and Translational Studies, National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NIH Animal Center, USA. 3. Laboratory of Comparative Ethology, National Institutes of Health/National Institute of Child Health and Human Development, NIH Animal Center, USA. 4. Chemical Biology Research Branch, National Institute on Drug Abuse, 9800 Medical Center Drive, Bethesda, USA. 5. Center for Social and Affective Neuroscience, IKE, Linkoping Univ, Sweden.
Abstract
BACKGROUND: Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process. METHODS: Four young adult male rhesus macaques were given access to an 8.4% alcohol solution every other weekday (EOD; M, W, F), while four other young adult males were given the same solution every weekday (ED; M-F). Subjects were then administered a CRF1 antagonist, antalarmin. RESULTS: EOD increased alcohol intake by up to 50% over baseline, with a more pronounced increase immediately following reintroduction of alcohol. For the morning/daytime sessions, EOD subjects increased their consumption by 83% over baseline. Differences between ED and EOD schedules emerged quickly, and EOD-induced escalation resulted in pharmacologically active BAC's. EOD-induced alcohol consumption was insensitive to CRFR1 blockade by antalarmin, but subjects with high CSF levels of CRF were more responsive. CONCLUSIONS: Similar to what has been observed in rodents, intermittent access results in an escalation of voluntary alcohol drinking in non-human primates. In contrast to findings in rats, recruitment of the CRF system does not seem to be involved in the escalated alcohol drinking observed under these conditions, though individual differences in CRF system activity may play a role.
BACKGROUND: Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process. METHODS: Four young adult male rhesus macaques were given access to an 8.4% alcohol solution every other weekday (EOD; M, W, F), while four other young adult males were given the same solution every weekday (ED; M-F). Subjects were then administered a CRF1 antagonist, antalarmin. RESULTS: EOD increased alcohol intake by up to 50% over baseline, with a more pronounced increase immediately following reintroduction of alcohol. For the morning/daytime sessions, EOD subjects increased their consumption by 83% over baseline. Differences between ED and EOD schedules emerged quickly, and EOD-induced escalation resulted in pharmacologically active BAC's. EOD-induced alcohol consumption was insensitive to CRFR1 blockade by antalarmin, but subjects with high CSF levels of CRF were more responsive. CONCLUSIONS: Similar to what has been observed in rodents, intermittent access results in an escalation of voluntary alcohol drinking in non-human primates. In contrast to findings in rats, recruitment of the CRF system does not seem to be involved in the escalated alcohol drinking observed under these conditions, though individual differences in CRF system activity may play a role.
Authors: Andrea Cippitelli; Ruslan Damadzic; Erick Singley; Annika Thorsell; Roberto Ciccocioppo; Robert L Eskay; Markus Heilig Journal: Pharmacol Biochem Behav Date: 2011-10-20 Impact factor: 3.533
Authors: Christina S Barr; Scott A Chen; Melanie L Schwandt; Stephen G Lindell; Hui Sun; Stephen J Suomi; Markus Heilig Journal: Biol Psychiatry Date: 2010-01-01 Impact factor: 13.382
Authors: J S Dileep Kumar; Andrei Molotkov; Michael C Salling; Patrick Carberry; Jaya Prabhakaran; John Castrillon; Akiva Mintz Journal: Pharmacol Rep Date: 2021-09-07 Impact factor: 3.024
Authors: Martin Henry Plawecki; Kurt White; Ann E K Kosobud; Nicholas Grahame; Ulrich S Zimmermann; David Crabb; Sean O'Connor Journal: Alcohol Clin Exp Res Date: 2018-08-29 Impact factor: 3.455