The specific aims of the research are to: 1. Continue to characterize the acute effects of delta-9-THC on auditory evoked neural activity in the dentate gyrus of the unanesthetized behaving rat. These experiments consist of dose-response analyses of the effects of delta-9-THC on synaptically identified auditory evoked potentials and dentate granule cell single unit discharges during the performance of both simple and complex auditory discrimination tasks. 2. Initiate studies on the effects of repeated daily administration of low and high doses of delta-9-THC on auditory evoked activity in the dentate gyrus, and dentate g-cell activity during prolonged performance of the auditory discrimination task. In these experiments we will determine whether tolerance to the acute effects of delta-9-THC develops with respect to these measures following either low or high doses of the drug when given repeatedly over several days. Specialized analyses of trial-by-trial variations in amplitude of these evoked responses indicate that event related correlates of cognitive processes may be altered by high dose levels of delta-9-THC. 3. Determine the effects of withdrawal from long-term exposure to both low and high doses of THC on the auditory evoked dentate gyrus neural activity. In addition, investigations of residual effects of delta-9-THC on these neurobehavioral correlates will also be examined following prolonged exposure to very high dose levels.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA003502-03
Application #
3207967
Study Section
(BPNB)
Project Start
1984-01-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Deadwyler, Sam A; Goonawardena, Anushka V; Hampson, Robert E (2007) Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol 18:571-80
Deadwyler, Sam A; Hampson, Robert E (2006) Temporal coupling between subicular and hippocampal neurons underlies retention of trial-specific events. Behav Brain Res 174:272-80
Zhuang, Shou-Yuan; Bridges, Daniel; Grigorenko, Elena et al. (2005) Cannabinoids produce neuroprotection by reducing intracellular calcium release from ryanodine-sensitive stores. Neuropharmacology 48:1086-96
Zhuang, S; Hampson, R E; Deadwyler, S A (2005) Behaviorally relevant endocannabinoid action in hippocampus: dependence on temporal summation of multiple inputs. Behav Pharmacol 16:463-71
Howlett, Allyn C; Breivogel, Christopher S; Childers, Steven R et al. (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47 Suppl 1:345-58
Deadwyler, Sam A; Hampson, Robert E (2004) Differential but complementary mnemonic functions of the hippocampus and subiculum. Neuron 42:465-76
Deadwyler, Sam A; Hayashizaki, Seiji; Cheer, Joseph et al. (2004) Reward, memory and substance abuse: functional neuronal circuits in the nucleus accumbens. Neurosci Biobehav Rev 27:703-11
Hampson, Robert E; Simeral, John D; Kelly, Erica J et al. (2003) Tolerance to the memory disruptive effects of cannabinoids involves adaptation by hippocampal neurons. Hippocampus 13:543-56
Kelly, Michele P; Deadwyler, Sam A (2003) Experience-dependent regulation of the immediate-early gene arc differs across brain regions. J Neurosci 23:6443-51
Hampson, Robert E; Deadwyler, Sam A (2003) Temporal firing characteristics and the strategic role of subicular neurons in short-term memory. Hippocampus 13:529-41

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