Ontogenetic changes in ethanol's motivational properties: Involvement of the kapp

Summary

Principal Investigator: Michael E Nizhnikov
Abstract: 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.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats
    María Belén Acevedo
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Córdoba C P 5000, Argentina Electronic address
    Behav Brain Res 265:203-15. 2014
  2. pmc Central effects of ethanol interact with endogenous mu-opioid activity to control isolation-induced analgesia in maternally separated infant rats
    Michael E Nizhnikov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902 6000, United States Electronic address
    Behav Brain Res 260:119-30. 2014
  3. pmc Prenatal ethanol exposure increases ethanol intake and reduces c-Fos expression in infralimbic cortex of adolescent rats
    Maria Carolina Fabio
    Instituto de Investigación Médica M y M Ferreyra, INIMEC CONICET, Universidad Nacional de Cordoba, Cordoba, C P 5000, Argentina
    Pharmacol Biochem Behav 103:842-52. 2013
  4. pmc μ-Opioid blockade reduces ethanol effects on intake and behavior of the infant rat during short-term but not long-term social isolation
    Andrey P Kozlov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, New York 13902 6000, United States
    Pharmacol Biochem Behav 103:773-82. 2013
  5. pmc Prenatal ethanol exposure leads to greater ethanol-induced appetitive reinforcement
    Ricardo M Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina Facultad de Psicología, Universidad Nacional de Cordoba, Cordoba, C P 5000, Argentina
    Alcohol 46:585-93. 2012
  6. pmc Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion
    María Belén Acevedo
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Friuli 2434, Cordoba, C P 5000, Argentina
    Dev Psychobiol 55:429-42. 2013
  7. pmc Early role of the κ opioid receptor in ethanol-induced reinforcement
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Physiol Behav 105:1231-41. 2012
  8. pmc Ontogenetic differences in ethanol's motivational properties during infancy
    Michael E Nizhnikov
    Center for Development and Behavioral Neuroscience, Binghamton University, NY 13902 6000, USA
    Alcohol 46:225-34. 2012
  9. pmc Early maternal separation affects ethanol-induced conditioning in a nor-BNI insensitive manner, but does not alter ethanol-induced locomotor activity
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Pharmacol Biochem Behav 100:630-8. 2012
  10. pmc The role of social isolation in ethanol effects on the preweanling rat
    Andrey P Kozlov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902 6000, United States
    Behav Brain Res 227:43-57. 2012

Scientific Experts

  • Ricardo Marcos Pautassi
  • Michael E Nizhnikov
  • Norman E Spear
  • Andrey P Kozlov
  • María Belén Acevedo
  • Elena I Varlinskaya
  • Juan C Molina
  • Tatiana A Kramskaya
  • Maria Carolina Fabio
  • Juan Carlos Molina
  • Samanta M March
  • Pouyan Rahmani

Detail Information

Publications15

  1. pmc Relationship between ethanol-induced activity and anxiolysis in the open field, elevated plus maze, light-dark box, and ethanol intake in adolescent rats
    María Belén Acevedo
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Córdoba C P 5000, Argentina Electronic address
    Behav Brain Res 265:203-15. 2014
    ..These results indicate that the OF is a valid procedure for the measurement of ethanol-induced stimulation, and provide information toward characterizing subpopulations of adolescents at risk for initiating alcohol drinking...
  2. pmc Central effects of ethanol interact with endogenous mu-opioid activity to control isolation-induced analgesia in maternally separated infant rats
    Michael E Nizhnikov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902 6000, United States Electronic address
    Behav Brain Res 260:119-30. 2014
    ..5 g/kg ethanol that decreases behaviors otherwise competing with independent ingestive activity...
  3. pmc Prenatal ethanol exposure increases ethanol intake and reduces c-Fos expression in infralimbic cortex of adolescent rats
    Maria Carolina Fabio
    Instituto de Investigación Médica M y M Ferreyra, INIMEC CONICET, Universidad Nacional de Cordoba, Cordoba, C P 5000, Argentina
    Pharmacol Biochem Behav 103:842-52. 2013
    ..Future studies should analyze the functionality of medial prefrontal cortex after prenatal ethanol and its potential association with predisposition for heightened ethanol intake...
  4. pmc μ-Opioid blockade reduces ethanol effects on intake and behavior of the infant rat during short-term but not long-term social isolation
    Andrey P Kozlov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, New York 13902 6000, United States
    Pharmacol Biochem Behav 103:773-82. 2013
    ..CTOP by itself did not affect IIA or saccharin intake in sober animals. The findings of the present experiments indicate that the anxiolytic effects of 0.5 g/kg ethanol on pups exposed to STSI are modulated by endogenous opioid activity...
  5. pmc Prenatal ethanol exposure leads to greater ethanol-induced appetitive reinforcement
    Ricardo M Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina Facultad de Psicología, Universidad Nacional de Cordoba, Cordoba, C P 5000, Argentina
    Alcohol 46:585-93. 2012
    ..This shift in the motivational reactivity to ethanol may be an underlying basis of the effect of prenatal ethanol on later ethanol acceptance...
  6. pmc Ethanol-induced locomotor activity in adolescent rats and the relationship with ethanol-induced conditioned place preference and conditioned taste aversion
    María Belén Acevedo
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Friuli 2434, Cordoba, C P 5000, Argentina
    Dev Psychobiol 55:429-42. 2013
    ..These measures of ethanol reinforcement, however, were not related to ethanol-induced LMA. Spontaneous LMA in an open field was, however, negatively associated with ethanol-induced CTA...
  7. pmc Early role of the κ opioid receptor in ethanol-induced reinforcement
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Physiol Behav 105:1231-41. 2012
    ..Overall, the results support the hypothesis that a reduced function of the KOR system in nondependent subjects should attenuate the aversive consequences of ethanol...
  8. pmc Ontogenetic differences in ethanol's motivational properties during infancy
    Michael E Nizhnikov
    Center for Development and Behavioral Neuroscience, Binghamton University, NY 13902 6000, USA
    Alcohol 46:225-34. 2012
    ..These results illustrate an ontogenetic change in the motivational properties of ethanol, with sensitivity to its appetitive properties declining and responsiveness to the aversive properties increasing with age during early infancy...
  9. pmc Early maternal separation affects ethanol-induced conditioning in a nor-BNI insensitive manner, but does not alter ethanol-induced locomotor activity
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Pharmacol Biochem Behav 100:630-8. 2012
    ..These results indicate that, when assessed in infant rats, earlier maternal separation alters the balance between the appetitive and aversive motivational effects of ethanol but has no effect on the motor activating effects of the drug...
  10. pmc The role of social isolation in ethanol effects on the preweanling rat
    Andrey P Kozlov
    Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY 13902 6000, United States
    Behav Brain Res 227:43-57. 2012
    ..Furthermore, differential reactivity of P12 males and females to STSI plays an important role in ethanol effects observed at this age...
  11. ncbi Ethanol-mediated appetitive conditioning in infant rats, but not corticosterone release, is dependent on route of ethanol administration
    Ricardo Marcos Pautassi
    Instituto de Investigaciones Médicas M y M Ferreyra INIMEC CONICET, Friuli 2434, Cordoba, Cba 5016, Argentina
    Dev Psychobiol 54:98-104. 2012
    ..The results confirm the differing motivational effects associated with i.g. and i.p. ethanol. These effects do not seem to be related to differential corticosterone responsiveness...
  12. pmc Ontogeny of ethanol intake in alcohol preferring (P) and alcohol nonpreferring (NP) rats
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Dev Psychobiol 53:234-45. 2011
    ..These results help to clarify the ontogeny of genetic predisposition for ethanol. Genetic predisposition for higher ethanol intake in P than in NP rats seems to be present immediately following birth...
  13. pmc An acetaldehyde-sequestering agent inhibits appetitive reinforcement and behavioral stimulation induced by ethanol in preweanling rats
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Pharmacol Biochem Behav 97:462-9. 2011
    ..These effects seem to be mediated by the first metabolite of ethanol, acetaldehyde...
  14. pmc Naloxone blocks ethanol-mediated appetitive conditioning and locomotor activation in adolescent rats
    Ricardo Marcos Pautassi
    Instituto de Investigación Médica M y M Ferreyra INIMEC CONICET, Cordoba, C P 5000, Argentina
    Behav Brain Res 216:262-9. 2011
    ..The present study indicates that adolescent rats are sensitive to ethanol's reinforcing and locomotor-stimulating effects. Both effects of ethanol appear to be mediated by endogenous opioid system activation...