Our previous studies demonstrate that prenatal ethanol exposure produces a persistent reduction in the electrical activity of midbrain dopamine neurons and alters dopamine receptor sensitivity. These changes are normalized by DA agonist administration. Midbrain DA neurotransmission is involved in many important CNS functions including reward, motor control attention, and locomotor activity. Therefore, prenatal ethanol exposure-induced dopamine hypofunction may contribute to the attention/hyperactivity problems commonly observed in children with fetal alcohol effects, fetal alcohol syndrome (FAE/FAS). In the proposed studies, we will use extracellular and intracellular electrophysiological recording techniques to further characterize the postnatal developmental process of dopamine systems that prenatal ethanol exposure. We will study how these changes may be normalized by dopamine agonists. We will also initiate behavioral experiments to correlate dopamine hypofunction and attention problems. In addition, the cellular leading to a reduction in the electrical activity of dopamine neurons after prenatal ethanol exposure will be examined. The results of these studies will better our understanding in the etiology of behavioral symptoms in FAE/FAS and help us to develop more appropriate animal models to advance the pharmacological treatment of FAE/FAS.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA012435-03
Application #
6168518
Study Section
Special Emphasis Panel (ZRG1-ALTX-3 (01))
Program Officer
Foudin, Laurie L
Project Start
1999-04-01
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
2000
Total Cost
$223,873
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Organized Research Units
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Wang, Ruixiang; Hausknecht, Kathryn A; Shen, Ying-Ling et al. (2018) Environmental enrichment reverses increased addiction risk caused by prenatal ethanol exposure. Drug Alcohol Depend 191:343-347
Wang, Ruixiang; Hausknecht, Kathryn A; Haj-Dahmane, Samir et al. (2018) Decreased environmental complexity during development impairs habituation of reinforcer effectiveness of sensory stimuli. Behav Brain Res 337:53-60
Hausknecht, Kathryn; Haj-Dahmane, Samir; Shen, Ying-Ling et al. (2015) Excitatory synaptic function and plasticity is persistently altered in ventral tegmental area dopamine neurons after prenatal ethanol exposure. Neuropsychopharmacology 40:893-905
Hausknecht, Kathryn; Haj-Dahmane, Samir; Shen, Roh-Yu (2013) Prenatal stress exposure increases the excitation of dopamine neurons in the ventral tegmental area and alters their reponses to psychostimulants. Neuropsychopharmacology 38:293-301
Marinetti, Laureen J; Leavell, Bonita J; Jones, Calleen M et al. (2012) Gamma butyrolactone (GBL) and gamma valerolactone (GVL): similarities and differences in their effects on the acoustic startle reflex and the conditioned enhancement of startle in the rat. Pharmacol Biochem Behav 101:602-8
Haj-Dahmane, Samir; Shen, Roh-Yu (2011) Modulation of the serotonin system by endocannabinoid signaling. Neuropharmacology 61:414-20
Haj-Dahmane, Samir; Shen, Roh-Yu (2010) Regulation of plasticity of glutamate synapses by endocannabinoids and the cyclic-AMP/protein kinase A pathway in midbrain dopamine neurons. J Physiol 588:2589-604
Haj-Dahmane, Samir; Shen, Roh-Yu (2009) Endocannabinoids suppress excitatory synaptic transmission to dorsal raphe serotonin neurons through the activation of presynaptic CB1 receptors. J Pharmacol Exp Ther 331:186-96
Muschamp, John W; Dominguez, Juan M; Sato, Satoru M et al. (2007) A role for hypocretin (orexin) in male sexual behavior. J Neurosci 27:2837-45
Shen, Roh-Yu; Choong, Kar-Chan; Thompson, Alexis C (2007) Long-term reduction in ventral tegmental area dopamine neuron population activity following repeated stimulant or ethanol treatment. Biol Psychiatry 61:93-100

Showing the most recent 10 out of 20 publications