zed the effects of prenatal marijuana exposure on cognitive function in children as negatively impacting aspects of executive function (EF). Tasks that required planning, integration, analysis and synthesis in addition to basic visuoperceptual abilities were impaired in children of marijuana-smoking women. Since these abilities develop over the early life of an individual, this proposal will address the effects of marijuana's major psychoactive constituent, delta9 tetrahydrocannabinol or delta9THC, on the development of these aspects of executive function in the rat. Four exposure periods will be studied and EF will be determined using 1) Active Place Avoidance, 2) Spatial navigation (radial arm maze with delay), 3) passive avoidance and 4) a novel attentional test. The overall hypothesis is that delta9THC exposure during the development of the circuits involved in each of these cognitive tasks (the mPFCx, hippocampus, MD thalamus, VTA etc) will impair specific aspects of executive function.
AIM I. Determine the effects of prenatal delta9THC on performance in EF tasks assessed in adulthood and compared to chronic delta9THC exposure in adults.
AIM II. Determine the effects of early postnatal (relevant to the latter half of human pregnancy) delta9THC exposure on performance of EF tasks in adulthood.
AIM III. Determine the effects of childhood/early adolescence delta9THC exposure on performance in EF tasks in adulthood.
AIM I V. Determine the effects of late adolescent/young adult delta9THC exposure on performance in EF tasks in adulthood.
AIM V. Determine the pattern of functional coupling that occurs in a normal rat engaged in an EF task using deoxyglucose and whether delta9THC exposure during critical periods of development will alter that pattern of functional coupling. In addition, the molecular underpinnings for these functional changes will be assessed using in situ hybridization histochemistry. Together, these studies will determine the effects of delta9THC exposure during early life on executive function and whether these exposures alter the pattern of functional coupling in brain when a subject is engaged in a cognitive task.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA019348-04
Application #
7284987
Study Section
Special Emphasis Panel (ZDA1-MXG-S (21))
Program Officer
Wetherington, Cora Lee
Project Start
2004-09-30
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
4
Fiscal Year
2007
Total Cost
$352,644
Indirect Cost
Name
Suny Downstate Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Dow-Edwards, Diana; Frank, Ashley; Wade, Dean et al. (2016) Sexually-dimorphic alterations in cannabinoid receptor density depend upon prenatal/early postnatal history. Neurotoxicol Teratol 58:31-39
Silva, Lindsay; Harte-Hargrove, Lauren; Izenwasser, Sari et al. (2015) Sex-specific alterations in hippocampal cannabinoid 1 receptor expression following adolescent delta-9-tetrahydrocannabinol treatment in the rat. Neurosci Lett 602:89-94
Harte-Hargrove, Lauren C; Dow-Edwards, Diana L (2012) Withdrawal from THC during adolescence: sex differences in locomotor activity and anxiety. Behav Brain Res 231:48-59
Silva, Lindsay; Zhao, Ning; Popp, Susanna et al. (2012) Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat. Neurotoxicol Teratol 34:63-71
Dow-Edwards, Diana (2011) Translational issues for prenatal cocaine studies and the role of environment. Neurotoxicol Teratol 33:9-16
Dow-Edwards, Diana (2010) Sex differences in the effects of cocaine abuse across the life span. Physiol Behav 100:208-15
Harte, Lauren C; Dow-Edwards, Diana (2010) Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat. Neurotoxicol Teratol 32:515-24
Dow-Edwards, Diana; Zhao, Ning (2008) Oral THC produces minimal behavioral alterations in preadolescent rats. Neurotoxicol Teratol 30:385-9