Neural Activity Related to Drug Craving in Cocaine Addiction

Kilts, Clinton D.; Schweitzer, Julie B.; Quinn, Colin; Gross, Robin E.; Faber, Tracy L.; Muhammad, Faheemah; Ely, Timothy D.; Hoffman, John M.; Drexler, Karen

doi:10.1001/archpsyc.58.4.334

Cited by 511 publications

(411 citation statements)

References 38 publications

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“…[2][3][4][5] In humans, neuroimaging studies have revealed cocaine-induced functional activation of the NAc following acute drug administration in cocaine-dependent subjects 6 and bilateral activation of the NAc following imagery-induced drug craving. [6][7][8] These data support numerous studies in animal models demonstrating the role of the NAc in the reinforcing effects of cocaine. [9][10][11][12][13][14] Although regional and neurotransmitter-centric hypotheses have provided a framework for studying the acute and chronic effects of cocaine intake on the brain, detailed mechanisms of intracellular neuroadaptations have only recently become known.…”

Section: Introductionsupporting

confidence: 79%

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

2006

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Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in the nucleus accumbens (NAc), a brain region associated with drug reinforcement. Two-dimensional gel electrophoresis was used to compare protein alterations in the NAc between cocaine overdose (COD) victims (n = 10) and controls (n = 10). Following image normalization, spots with significantly differential image intensities (P < 0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight. A total of 1407 spots were found to be present in a minimum of five subjects per group and the intensity of 18 spots was found to be differentially abundant between the groups, leading to positive identification of 15 proteins by peptide mass fingerprinting (PMF). Of an additional 37 protein spots that were constitutively expressed, 32 proteins were positively identified by PMF. Increased proteins in COD included b-tubulin, liprin-a3 and neuronal enolase, whereas decreased proteins included parvalbumin, ATP synthase b-chain and peroxiredoxin 2. The present data provide a preliminary protein profile of COD, suggesting the involvement of novel proteins and pathways in the expression of this complex disease. Additional studies are warranted to further characterize alterations in the differentially regulated proteins. Understanding the coordinated involvement of multiple proteins in cocaine abuse provides insight into the molecular basis of the disease and offers new targets for pharmacotherapeutic intervention for drug abuse-related disorders.

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Section: Introductionsupporting

confidence: 79%

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

2006

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“…The amygdala is one of the few brain regions that consistently exhibit increased metabolic activity in response to cocaine-associated cues in both animal (Brown et al, 1992;Ciccocioppo et al, 2001) and human (Childress et al, 1999;Kilts et al, 2001) studies, consistent with this region's role in conditioned emotional memories. In preclinical studies, the infusion of scopolamine into the BLA just prior to the acquisition phase of a classical conditioning procedure produced a dose-dependent disruption of cocaine-seeking behavior during cue-induced drug reinstatement (See et al, 2003).…”

Section: Acetylcholine and Conditioned Learningmentioning

confidence: 59%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

163

138

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Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

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“…These include various portions of the cingulate gyrus (Breiter et al, 1997;Childress et al, 1999;Garavan et al, 2000;Grant et al, 1996;Kilts et al, 2001;Mass et al, 1998;Wexler et al, 2001;Brody et al, 2002), the orbital cortex (Grant et al, 1996;Mass et al, 1998;Wang et al, 1999), the nucleus accumbens (Breiter et al, 1997;George et al, 2001;Kilts et al, 2001), and the insula (Breiter et al, 1997;Wang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Differential Brain Activity in Alcoholics and Social Drinkers to Alcohol Cues: Relationship to Craving

Myrick

Anton

et al. 2003

Neuropsychopharmacol

472

345

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Using fMRI, our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures, alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus. This study extends this earlier work with several improvements including imaging the entire brain (rather than the anterior half previously) and recording craving, while the subjects viewed images within the scanner. In a Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min randomized presentation of pictures of alcoholic beverages, nonalcoholic beverages, and two different visual control tasks. During picture presentation, changes in regional brain activity were measured in 15 transverse T2*-weighted blood oxygen level dependent slices. Subjects rated their urge to drink after each picture sequence. After a sip of alcohol, while viewing alcohol cues compared to viewing other beverage cues, the alcoholics, but not social drinkers, reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions. Brain activity in the left nucleus accumbens, anterior cingulate, and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects. This study suggests, as did our earlier study, that alcoholics and not social drinkers, when exposed to alcohol cues, have increased brain activity in areas that reportedly subserve craving for other addictive substances.

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Neural Activity Related to Drug Craving in Cocaine Addiction

Cited by 511 publications

References 38 publications

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

The Role of Acetylcholine in Cocaine Addiction

Differential Brain Activity in Alcoholics and Social Drinkers to Alcohol Cues: Relationship to Craving

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