The objective of Project #3 """"""""Consequences of chronic exposure to A9-tetrahydrocannabinol in monkeys"""""""" is to further the goals of the P20 center by establishing a model of adolescent cannabis exposure in nonhuman primates. The studies propose to examine the neurobehavioral and neurochemical sequelae of chronic exposure to A9-tetrahydrocannabinol (THC) in peri-adolescent rhesus monkeys. The model offers a unique translational bridge across the Center Projects because monkeys will be studied across the adolescent (Proj #2) to young adult (Proj #1) developmental stages, will be examined on tasks identical in many cases to the human tasks and can be exposed to specific drug models informed by Proj #4 rodent results.
The first Aim i s to determine the effects of chronic THC exposure on neuropsychological test battery measures (CANTAB) long established in the laboratory. The acquisition and performance of tasks which measure attentional shift, spatial memory, recognition memory, decision making motor function and motivation will be compared between animals chronically exposed to THC for 2 years and vehicle-exposed monkeys. Since CANTAB measures will also be employed in Proj #1 and #2, and analogous tasks used in the rodent Proj #4, the results from the monkeys will be used to refine the specificity of the behavioral measures for all projects. Periodic cerebrospinal fluid sampling will be employed throughout chronic dosing to monitor neurochemical sequelae of chronic exposure.
The second Aim i s to determine the effects of withdrawal from chronic THC exposure on behavior, neurochemistry and physiology;antagonist challenge (SR141716A) and spontaneous (28 day) withdrawal approaches will be examined.
The fourth Aim i s to determine the effects of chronic THC exposure on brain activation using functional Magnetic Resonance Imaging. This f MRI approach is developmental in nature and will be informed by ongoing results from Proj #1 and #2. In total, the studies proposed will address questions regarding the impact of chronic exposure to the primary psychoactive constituent of cannabis and the behavioral specificity, neurochemical and neurovascular sequelae of chronic THC in monkeys will be determined. These studies will also establish a peri-adolescent model of cannabis exposure with tremendous potential for further translational studies in an eventual full Center.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
5P20DA024194-04
Application #
8106374
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$223,550
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A (2015) Cannabidiol fails to reverse hypothermia or locomotor suppression induced by ?(9) -tetrahydrocannabinol in Sprague-Dawley rats. Br J Pharmacol 172:1783-91
Taffe, M A (2015) Drug abuse scientists should use social media to engage the public because their primary translational product is information. Drug Alcohol Depend 154:315-9
Irimia, Cristina; Polis, Ilham Y; Stouffer, David et al. (2015) Persistent effects of chronic ?9-THC exposure on motor impulsivity in rats. Psychopharmacology (Berl) 232:3033-43
Jacobus, Joanna; Squeglia, Lindsay M; Sorg, Scott F et al. (2014) Cortical thickness and neurocognition in adolescent marijuana and alcohol users following 28 days of monitored abstinence. J Stud Alcohol Drugs 75:729-43
Hanson, Karen L; Thayer, Rachel E; Tapert, Susan F (2014) Adolescent marijuana users have elevated risk-taking on the balloon analog risk task. J Psychopharmacol 28:1080-7
Wright Jr, M Jerry; Vandewater, Sophia A; Taffe, Michael A (2013) Cannabidiol attenuates deficits of visuospatial associative memory induced by ?(9) tetrahydrocannabinol. Br J Pharmacol 170:1365-73
Wetherill, Reagan; Tapert, Susan F (2013) Adolescent brain development, substance use, and psychotherapeutic change. Psychol Addict Behav 27:393-402
Mahmood, O M; Goldenberg, D; Thayer, R et al. (2013) Adolescents' fMRI activation to a response inhibition task predicts future substance use. Addict Behav 38:1435-41
Wright Jr, M J; Vandewater, S A; Parsons, L H et al. (2013) ?(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. Neuroscience 235:51-8
Jacobus, Joanna; Goldenberg, Diane; Wierenga, Christina E et al. (2012) Altered cerebral blood flow and neurocognitive correlates in adolescent cannabis users. Psychopharmacology (Berl) 222:675-84

Showing the most recent 10 out of 35 publications