Fetal alcohol exposure in humans is recognized as a likely contributor to alcohol abuse during adolescence and adulthood. Exposure to ethanol in laboratory rodents during the first two postnatal weeks is widely used as an experimental model of human fetal alcohol exposure, given its accepted value as a neurological model for the third trimester of human fetal development. Such early exposure has been shown to significantly increase ethanol intake later in life. The neural mechanisms susceptible to early ethanol exposure and responsible for the reported increased propensity for ethanol intake are yet to be investigated. The endogenous dynorphin/kappa opioid receptor system is of great interest due to its possible involvement in diminishing ethanol intake through modulation of its aversive properties. There is some experimental evidence, although still limited, that motivational properties of the dynorphin/kappa opioid receptor system change across ontogeny, with newborn and infant rats finding activation of kappa opioid receptors appetitive and adult rats demonstrating aversive responding. These findings, in turn, suggest ontogenetic differences in the kappa opioid receptor involvement in ethanol intake and reinforcement based, presumably, on ontogenetic changes in motivational properties of the dynorphin/ kappa opioid receptor system. The present proposal will test the hypothesis that the motivational properties of the kappa opioid system switch from appetitive to aversive during the 2nd postnatal week, with this switch being parallel to an ontogenetic increase in sensitivity to the aversive properties of ethanol. Exposure to ethanol early in life, especially during the period when the dynorphin/kappa opioid receptor system functions to mediate appetitive reinforcement, alters the aversive motivational properties of this system, with this alteration contributing to the propensity to consume large amounts of ethanol without experiencing its aversive consequences later in ontogeny.

Public Health Relevance

Exposure to alcohol early in life is a major contributing factor to future use and abuse of the drug. The kappa/dynorphin opioid system seems to be critically involved in modulating the aversive properties of ethanol during adulthood. The function of this system may change as a result of early alcohol exposure. The proposed experiments will dissect the changes in the motivational properties of ethanol and the kappa/dynorphin system across the first two weeks of life. Furthermore, these studies will investigate possible effect of early ethanol exposure on the motivational properties of ethanol and kappa opioid system.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA018164-02
Application #
7862617
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Grakalic, Ivana
Project Start
2009-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$227,609
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
Kamenetzky, Giselle V; Suárez, Andrea B; Pautassi, Ricardo M et al. (2015) Change in the hedonic value of an aversive stimulus in the presence of a pre-exposed odor. Physiol Behav 148:51-7
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
Nizhnikov, Michael E; Pautassi, Ricardo M; Carter, Jenna M et al. (2014) Brief prenatal ethanol exposure alters behavioral sensitivity to the kappa opioid receptor agonist (U62,066E) and antagonist (Nor-BNI) and reduces kappa opioid receptor expression. Alcohol Clin Exp Res 38:1630-8
Acevedo, María Belén; Nizhnikov, Michael E; Molina, Juan C et al. (2014) Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats. Behav Brain Res 265:203-15
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
Acevedo, María Belén; Nizhnikov, Michael E; Spear, Norman E et al. (2013) Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion. Dev Psychobiol 55:429-42
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
Fabio, Maria Carolina; March, Samanta M; Molina, Juan Carlos et al. (2013) Prenatal ethanol exposure increases ethanol intake and reduces c-Fos expression in infralimbic cortex of adolescent rats. Pharmacol Biochem Behav 103:842-52
Kozlov, Andrey P; Nizhnikov, Michael E; Varlinskaya, Elena I et al. (2012) The role of social isolation in ethanol effects on the preweanling rat. Behav Brain Res 227:43-57
Nizhnikov, Michael E; Pautassi, Ricardo Marcos; Varlinskaya, Elena I et al. (2012) Ontogenetic differences in ethanol's motivational properties during infancy. Alcohol 46:225-34

Showing the most recent 10 out of 18 publications