Many dysfunctional aspects of drug abuse can be understood and effectively treated only when the links between changes in levels of neuromodulators, sleep, and cognition are well described and analyzed. This proposal focuses on the cognitive effects of two drug classes, the psychostimulants (here cocaine) and the selective serotonin reuptake inhibitors or SSRIs (here paroxetine), both of which are known to potentiate the monoaminergic neuronal systems of the brain. Drawing upon our basic neurobiological knowledge and theories of sleep and cognition, we have generated specific predictions on the sleep and neuromodulatory factors mediating the cognitive effects of cocaine abuse. We will combine our validated ambulatory sleep monitor, the Nightcap, with cognitive tests that can be presented and performed on the same Macintosh computer that analyzes sleep measurements. The study of drug effects on sleep and cognition will be made considerably more economical and naturalistic by the application of this integrated ambulatory system. We plan to use this ambulatory monitoring capability at two unique research facilities, the cocaine self-administration laboratory of the Substance Use Research Center at Columbia Medical School and the Harvard Laboratory of Neurophysiology sleep laboratory, to study how sleep, monoaminergic mechanisms, and their interactions may mediate the cognitive sequelae of cocaine abuse. At the heart of this proposal is the idea that the monoaminergic drugs of abuse such as cocaine, first potentiate but then later impair the neuromodulatory dynamics of the wake-sleep cycle with ultimately deleterious effects upon cognitive functioning. We propose a series of studies which are theory-driven and which test specific hypotheses that will allow us to isolate and describe the interrelated effects of sleep and monoaminergic neuromodulators on the known negative cognitive effects of cocaine use and abstinence. In a set of seven complementary protocols, we will compare the individual and combined effects on sleep and cognitive performance of repeated cocaine administration and abstinence, administration and discontinuation of paroxetine, and REM sleep deprivation. The proposed research will answer fundamental questions regarding the cognitive benefits of sleep and how these benefits are lost when drugs are abused.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA011744-02
Application #
6174753
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Gordon, Harold
Project Start
1999-09-01
Project End
2003-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
2
Fiscal Year
2000
Total Cost
$344,945
Indirect Cost
Name
Massachusetts Mental Health Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Hodges, Sarah E; Pittman, Brian; Morgan, Peter T (2017) Sleep Perception and Misperception in Chronic Cocaine Users During Abstinence. Sleep 40:
Angarita, Gustavo A; Emadi, Nazli; Hodges, Sarah et al. (2016) Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review. Addict Sci Clin Pract 11:9
Morgan, Peter T; Angarita, Gustavo A; Canavan, Sofija et al. (2016) Modafinil and sleep architecture in an inpatient-outpatient treatment study of cocaine dependence. Drug Alcohol Depend 160:49-56
Angarita, Gustavo A; Canavan, Sofija V; Forselius, Erica et al. (2014) Correlates of polysomnographic sleep changes in cocaine dependence: self-administration and clinical outcomes. Drug Alcohol Depend 143:173-80
Canavan, Sofija V; Forselius, Erica L; Bessette, Andrew J et al. (2014) Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users. Addict Behav 39:1057-61
Angarita, G A; Canavan, S V; Forselius, E et al. (2014) Abstinence-related changes in sleep during treatment for cocaine dependence. Drug Alcohol Depend 134:343-347
Matuskey, D; Pittman, B; Chen, J I et al. (2012) A single-day paradigm of self-regulated human cocaine administration. Pharmacol Biochem Behav 103:95-101
Pace-Schott, Edward F; Shepherd, Elizabeth; Spencer, Rebecca M C et al. (2011) Napping promotes inter-session habituation to emotional stimuli. Neurobiol Learn Mem 95:24-36
Matuskey, D; Pittman, B; Forselius, E et al. (2011) A multistudy analysis of the effects of early cocaine abstinence on sleep. Drug Alcohol Depend 115:62-6
Angarita, Gustavo A; Pittman, Brian; Gueorguieva, Ralitza et al. (2010) Regulation of cocaine self-administration in humans: lack of evidence for loading and maintenance phases. Pharmacol Biochem Behav 95:51-5

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