In a recent double-blind placebo-controlled study we found the broad spectrum anticonvulsant zonisamide (ZON) to have effects on ethanol consumption that are comparable to those of topiramate. We hypothesize here that the administration of ZON, by attenuating the hyperexcitability of the brain during periods of abstinence, through its neuro-protective effects, and its enhancement of dopamine activity in midbrain and frontal regions will counteract the effects of alcohol that lead to impaired regulatio of emotional and reward processes that control the consumption of alcohol. This will be evident by the normalization of brain activity seen in performance of the alcohol and emotional-word Stroop tasks and in a reduction of the BOLD response to alcohol related images. The results of this study should provide an indication of the neurobehavioral mechanisms through which ZON may act to regulate the consumption of alcohol.

Public Health Relevance

The proposed research is relevant to the public health mission of NIAAA because it will use new methods of developing new medications for alcoholism treatment by identifying how zonisamide effects brain circuits regulatory alcohol intake and reward. Alcoholism is the third leading cause of preventable death in the US, with 80,000 deaths annually.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA015923-06
Application #
8990076
Study Section
Special Emphasis Panel (ZAA1-DD (03)M)
Program Officer
Fertig, Joanne
Project Start
2005-12-01
Project End
2021-06-30
Budget Start
2016-09-15
Budget End
2017-06-30
Support Year
6
Fiscal Year
2016
Total Cost
$764,086
Indirect Cost
$274,227
Name
Boston University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Devine, Eric G; Knapp, Clifford M; Sarid-Segal, Ofra et al. (2015) Payment expectations for research participation among subjects who tell the truth, subjects who conceal information, and subjects who fabricate information. Contemp Clin Trials 41:55-61
Knapp, Clifford M; Ciraulo, Domenic A; Sarid-Segal, Ofra et al. (2015) Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders. J Clin Psychopharmacol 35:34-42
Oldham, Mark A; Ciraulo, Domenic A (2014) Bright light therapy for depression: a review of its effects on chronobiology and the autonomic nervous system. Chronobiol Int 31:305-19
Knapp, Clifford M; Ciraulo, Domenic A; Datta, Subimal (2014) Mechanisms underlying sleep-wake disturbances in alcoholism: focus on the cholinergic pedunculopontine tegmentum. Behav Brain Res 274:291-301
Knapp, Clifford M; O'Malley, Matthew; Datta, Subimal et al. (2014) The Kv7 potassium channel activator retigabine decreases alcohol consumption in rats. Am J Drug Alcohol Abuse 40:244-50
Devine, Eric G; Waters, Megan E; Putnam, Megan et al. (2013) Concealment and fabrication by experienced research subjects. Clin Trials 10:935-48
Ciraulo, Domenic A; Barlow, David H; Gulliver, Suzy Bird et al. (2013) The effects of venlafaxine and cognitive behavioral therapy alone and combined in the treatment of co-morbid alcohol use-anxiety disorders. Behav Res Ther 51:729-35
Afshar, Maryam; Knapp, Clifford M; Sarid-Segal, Ofra et al. (2012) The efficacy of mirtazapine in the treatment of cocaine dependence with comorbid depression. Am J Drug Alcohol Abuse 38:181-6
Knapp, Clifford M; Sarid-Segal, Ofra; Richardson, Mark A et al. (2010) Open label trial of the tolerability and efficacy of zonisamide in the treatment of alcohol dependence. Am J Drug Alcohol Abuse 36:102-5
Streeter, Chris C; Whitfield, Theodore H; Owen, Liz et al. (2010) Effects of yoga versus walking on mood, anxiety, and brain GABA levels: a randomized controlled MRS study. J Altern Complement Med 16:1145-52

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