Alcohol is the number one abused substance among adolescents. Several studies have shown that when adolescents use alcohol, they become excessive users of alcohol, and of other substances of abuse, later in life. Adolescents differ from adults in their response to alcohol in exhibiting less sensitivity to the sedative and motor impairing effects. Adolescent rats exhibit more tolerance to alcohol-induced hypothermia, and greater impairments in spatial memory than adult rats. In adolescent rats, the N-methyI-D-aspartate (NMDA) receptor-mediated synaptic plasticity in the hippocampus is more sensitive to alcohol than adults. Although differences in alcohol sensitivity between adolescent and adult rats have been established, the temporal effect of acute and repeated alcohol exposure during the adolescent period on spatial learning and memory remains unknown. The goal of the proposed study is to investigate the short- and long-term effects of alcohol exposure during the adolescent period on spatial memory. Hypotheses to be tested are: (1) alcohol exposure in adolescent rats cause impairments in spatial memory, (2) behavioral effects of repeated alcohol exposure in adolescent rats are long-term, (3) behavioral effects of alcohol exposure in adolescent rats differ from those in immature and adult rats, and (4) deficits in adolescent alcohol-induced spatial memory are associated with alterations in the NMDA receptor-channel complex. Rats will be exposed to acute and repeated alcohol treatments during the adolescent period and tested for deficits in the reference and visual spatial memory tasks in the Morris Water Maze. Others have already identified specific interactions between alcohol and the major neurotransmitter systems such as glutamate, GABA, dopamine, serotonin, endogenous opioids. In this proposal, adolescent alcohol exposure on the NMDA receptor-channel complex will be investigated. The proposed studies will identify neuroadaptive changes of early alcohol exposure and define the plasticity of the central nervous system during the adolescent period.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA013396-04
Application #
6879966
Study Section
Special Emphasis Panel (ZAA1-DD (20))
Program Officer
Witt, Ellen
Project Start
2003-04-01
Project End
2008-03-31
Budget Start
2005-04-01
Budget End
2008-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$165,000
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Sircar, Ratna; Basak, Ashim K; Sircar, Debashish (2009) Repeated ethanol exposure affects the acquisition of spatial memory in adolescent female rats. Behav Brain Res 202:225-31
Sircar, Ratna; Sircar, Debashish (2006) Repeated ethanol treatment in adolescent rats alters cortical NMDA receptor. Alcohol 39:51-8
Sircar, Ratna; Sircar, Debashish (2005) Adolescent rats exposed to repeated ethanol treatment show lingering behavioral impairments. Alcohol Clin Exp Res 29:1402-10
Sircar, Ratna; Basak, Ashim (2004) Adolescent gamma-hydroxybutyric acid exposure decreases cortical N-methyl-D-aspartate receptor and impairs spatial learning. Pharmacol Biochem Behav 79:701-8