Use of ethanol during or just before adolescence clearly predicts ethanol abuse later in life. Is this ethanol use in adolescence due to still earlier exposure to ethanol? Epidemiological evidence in humans and experiments with rats indicate that ethanol acceptance in adolescence is potentiated by prenatal exposure to ethanol. The present proposal tests the hypothesis that a few moderate, nonteratological doses of ethanol during late gestation alters later responsiveness to ethanol, including ethanol acceptance and reinforcement from birth to adolescence and activating effects of ethanol during adolescence. This hypothesis is encouraged by preliminary studies indicating that this prenatal ethanol exposure not only increases later ethanol acceptance but also increases the range of appetitively reinforcing ethanol doses. In each of the proposed experiments postnatal responsiveness to ethanol will be assessed for animals given 0, 1 or 2 g/kg on each of gestational days 17-20 or a control treatment.
Specific Aim 1 is to test ethanol intake and ethanol reinforcement soon after birth, in terms of three different reinforcement paradigms.
Specific Aim 2 is to test effects of .prenatal ethanol on ethanol acceptance and ethanol reinforcement in adolescence and at a point midway between birth and adolescence (postnatal day 15, P15).
Specific Aim 3 is to test the consequences of prenatal ethanol exposure for an established activating effect of ethanol during adolescence, ethanol- induced social facilitation. In view of the apparent role of the endogenous opioid system in ethanol ingestion, ethanol reinforcement and adolescent social behavior, Specific Aim 4 is to test the effects of prenatal ethanol on beta-endorphin gene expression, beta-endorphin brain levels and ?-opioid receptor binding associated with ethanol ingestion, ethanol reinforcement, and ethanol-induced social behavior. These tests will occur soon after birth, on P15 or during adolescence. The intention is to clarify the ontogeny of risk from moderate exposure to prenatal ethanol and determine mechanisms underlying subsequently altered responsiveness to ethanol. *Proposed experiments will test the observation that individuals exposed to ethanol as fetuses are more likely to abuse ethanol as adolescents and adults, whether this fetal exposure makes ethanol more rewarding and acceptable later on, and how these effects might be mediated by the opiate system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA015992-04
Application #
7661709
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Witt, Ellen
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
4
Fiscal Year
2009
Total Cost
$311,577
Indirect Cost
Name
State University of NY, Binghamton
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Castelló, Stefanía; Molina, Juan Carlos; Arias, Carlos (2017) Long-term contextual memory in infant rats as evidenced by an ethanol conditioned tolerance procedure. Behav Brain Res 332:243-249
Macchione, A F; Anunziata, F; Culleré, M E et al. (2016) Conditioned breathing depression during neonatal life as a function of associating ethanol odor and the drug's intoxicating effects. Dev Psychobiol 58:670-86
Bordner, Kelly; Deak, Terrence (2015) Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period. Physiol Behav 148:100-10
Cullere, Marcela; Macchione, Ana Fabiola; Haymal, Beatriz et al. (2015) Neonatal sensitization to ethanol-induced breathing disruptions as a function of late prenatal exposure to the drug in the rat: modulatory effects of ethanol's chemosensory cues. Physiol Behav 139:412-22
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
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
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
Miranda-Morales, Roberto Sebastián; 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
Fabio, María 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
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

Showing the most recent 10 out of 61 publications