Postnatal ontogeny of ethanol ingestion and reinforcement in the rat will be studied between early infancy and adolescence toward determining the relationship between age-related changes in response to ethanol and corresponding changes in brain development. This relationship may help explain why modest exposure of fetus or infant to ethanol increases subsequent ethanol ingestion among rodents and risk for ethanol abuse in humans. Such an ontogenetic strategy has a productive history in behavioral neuroscience, provides an alternative to the successful strategy of testing brain- behavior relationships in rodents selected genetically for ethanol sensitivity, and, in view of evidence that adolescence is characterized by behaviors that promote alcohol abuse and alcoholism into adulthood, begins tests of whether ontogenetic progression into this aspect of adolescence is abrupt, a discrete break from earlier ages, or continuous. The first specific aim is to determine the ontogeny of ethanol ingestion and ethanol reinforcement in the rat between early infancy and adolescence.
Specific Aim 2 is to test the hypothesis that age-related peculiarities of ethanol ingestion and reinforcement between early infancy and adolescence are associated with ontogenetic change in brain opioid mechanisms. Among many other brain systems likely important for response to ethanol, one advantage of selecting the opioid systems for examination is the widespread clinical application of the opioid antagonist, naltrexone, in treatment of alcohol abuse.
Specific Aim 3 is to test ethanol ingestion during adolescence for animals that have been exposed to ethanol at different stages of earlier ontogeny, with or without a selective opioid antagonist. This may reveal sensitive periods during development at which ethanol exposure places the individual at special risk for later ethanol abuse, and may determine whether specific opioid antagonists at the time of early exposure decrease the likelihood of enhanced ethanol ingestion during adolescence.

Public Health Relevance

Adolescence is accompanied by behaviors such as excessive alcohol ingestion that risk life-long alcohol abuse. Clinical and experimental evidence indicates that earlier exposure to alcohol increases its ingestion in adolescence. Proposed experiments will track age-related change in alcohol ingestion and reinforcement between birth and adolescence, test associated influence of the opioid system, and determine potential sensitive periods prior to adolescence at which exposure to alcohol especially enhances adolescent ingestion of alcohol.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Witt, Ellen
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State University of NY, Binghamton
Schools of Arts and Sciences
United States
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Miranda-Morales, Roberto Sebastian; Nizhnikov, Michael E; Spear, Norman E (2014) Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats. Alcohol 48:19-23
Miranda-Morales, Roberto Sebastián; Nizhnikov, Michael E; Waters, Dustin H et al. (2014) New evidence of ethanol's anxiolytic properties in the infant rat. Alcohol 48:367-74
Fabio, Maria Carolina; Nizhnikov, Michael E; Spear, Norman E et al. (2014) Binge ethanol intoxication heightens subsequent ethanol intake in adolescent, but not adult, rats. Dev Psychobiol 56:574-83
Nizhnikov, Michael E; Kozlov, Andrey P; Kramskaya, Tatiana A et al. (2014) Central effects of ethanol interact with endogenous mu-opioid activity to control isolation-induced analgesia in maternally separated infant rats. Behav Brain Res 260:119-30
Culleré, Marcela Elena; Spear, Norman E; Molina, Juan Carlos (2014) Prenatal ethanol increases sucrose reinforcement, an effect strengthened by postnatal association of ethanol and sucrose. Alcohol 48:25-33
Miranda-Morales, Roberto Sebastian; Nizhnikov, Michael E; Waters, Dustin H et al. (2013) Participation of the nociceptin/orphanin FQ receptor in ethanol-mediated locomotor activation and ethanol intake in preweanling rats. Behav Brain Res 245:137-44
March, Samanta M; Abate, Paula; Spear, Norman E et al. (2013) The role of acetaldehyde in ethanol reinforcement assessed by Pavlovian conditioning in newborn rats. Psychopharmacology (Berl) 226:491-9
Revillo, D A; Arias, C; Spear, N E (2013) The unconditioned stimulus pre-exposure effect in preweanling rats in taste aversion learning: role of the training context and injection cues. Dev Psychobiol 55:193-204
March, Samanta M; Pautassi, Ricardo M; Nizhnikov, Michael et al. (2013) Olfactory preference for ethanol following social interaction with an intoxicated peer in adolescent rats exposed to ethanol in-utero. Psicothema 25:355-62
Kozlov, Andrey P; Nizhnikov, Michael E; Kramskaya, Tatiana A et al. (2013) ?-Opioid blockade reduces ethanol effects on intake and behavior of the infant rat during short-term but not long-term social isolation. Pharmacol Biochem Behav 103:773-82

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