Cocaine dependence: a disease of the brain’s reward centers

Dackis, Charles A.; O’Brien, Charles P.

doi:10.1016/s0740-5472(01)00192-1

Cited by 274 publications

(193 citation statements)

References 22 publications

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“…First, the anhedonic state often associated with use of stimulants may play a role in heightening vulnerability to suicidal behaviors. Supporting this presumption, several imaging studies reported dopamine hypoactivity among long-term cocaine and amphetamine users (Volkow et al, 2001;Volkow et al, 1997), which has been implicated in inducing a chronic state of anhedonia and heightened vulnerability to suicide (Dackis and O'Brien, 2001). A second possible explanation for our finding relates to the varying degrees of impulsivity seen across users of stimulants and opioids.…”

Section: Associations Of Stimulant Use Patterns With Suicide Attemptsupporting

confidence: 61%

Associations of substance use patterns with attempted suicide among persons who inject drugs: Can distinct use patterns play a role?

Artenie

Bruneau

Zang

et al. 2015

Drug and Alcohol Dependence

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Background: While the elevated risk of suicide attempt among persons who inject drugs (PWID) is well documented, whether use of different substances is associated with varying degrees of risk remains unclear. We sought to examine the associations between substance use patterns and attempted suicide in a prospective cohort of PWID in Montreal, Canada. Methods: Between 2004 and 2011, participants completed an interviewer-administered questionnaire eliciting information on socio-demographic, substance use patterns, related behaviors, and mental health markers. Generalized estimating equations were used to model the relationship between self-reported use of six common substances (cocaine, amphetamine, opioids, sedative-hypnotics, cannabis and alcohol), associated patterns of use (chronic, occasional and none), and a recent (past six-month) suicide attempt. Results: At baseline, of 1,240 participants (median age: 39.1, 83.7% male), 71 (5.7%) reported a recent suicide attempt. Among 5,621 observations collected during follow-up, 221 attempts were reported by 143 (11.5%) participants. In multivariate analyses adjusting for socio-demographic and psychosocial stressors, among primary drugs of abuse, chronic [Adjusted Odds Ratio (AOR): 1.97] and occasional (AOR: 1.92) cocaine use, and chronic amphetamine use (AOR: 1.96) were independently associated with attempted suicide. Among co-used substances, chronic sedative-hypnotic use was independently associated with an attempt (AOR: 2.29). No statistically significant association was found for the remaining substances. Conclusion: Among PWID at high risk of attempted suicide, stimulant users appear to constitute a particularly vulnerable sub-group. While the mechanisms underlying these associations remain to be elucidated, findings suggest that stimulant-using PWID should constitute a prime focus of suicide prevention efforts

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Section: Associations Of Stimulant Use Patterns With Suicide Attemptsupporting

confidence: 61%

Associations of substance use patterns with attempted suicide among persons who inject drugs: Can distinct use patterns play a role?

Artenie

Bruneau

Zang

et al. 2015

Drug and Alcohol Dependence

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“…One study (Klein et al, 1997) showed that methylphenidate, which stimulates the release of NE and DA, reduced antisocial behavior reports in children with CD independent of ADHD symptoms. Moreover, the knowledge that the reward system in the brain and DA are implicated in the neurobiology of addiction (Dackis & O'Brien, 2001) and that children with CD are at considerable risk of substance abuse (Kazdin, 1995) is consistent with an involvement of DA in the modulation of aggressive behavior in children. More research is needed to clarify the precise role of NE and DA in the instigation and regulation of aggressive behavior in children.…”

Section: Csf 5-hiaamentioning

confidence: 71%

The evidence for a neurobiological model of childhood antisocial behavior.

Goozen¹,

Fairchild²,

Snoek³

et al. 2007

Psychological Bulletin

412

393

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Children with persistent antisocial and aggressive behavior are diagnosed as having disruptive behavior disorder. The authors review evidence that antisocial children, and especially those who persist with this behavior as they grow older, have a range of neurobiological characteristics. It is argued that serotonergic functioning and stress-regulating mechanisms are important in explaining individual differences in antisocial behavior. Moreover, low fear of punishment and physiological underactivity may predispose antisocial individuals to seek out stimulation or take risks and may help to explain poor conditioning and socialization. The authors propose a theoretical model highlighting the interplay between neurobiological deficits and cognitive and emotional functioning as mediators of the link between early adversity and antisocial behavior problems in childhood. Implications for intervention programs are discussed.

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“…Understanding the neural and molecular mechanisms underlying ethanol addiction is crucial for the development of effective therapies for alcoholism. It is currently believed that the nucleus accumbens (NAcc) is critically involved in many drug-related behaviors (eg, (Badanich et al, 2006;Dackis and O'Brien, 2001;Di Chiara et al, 1993;Li and Kauer, 2004;Wenger et al, 2003)). It is well established that the central glutamate system is involved in significant neuro-adaptive changes in response to ethanol exposure (Flatscher-Bader et al, 2008;Kemppainen et al, 2010;Wills et al, 2012;Xiao et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

Bahí

2012

Neuropsychopharmacol

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Whether metabotropic glutamate 7 (mGluR7) -activation enhances or diminishes the reinforcing properties of psychostimulants remains unclear. We have previously shown that systemic mGluR7 activation reduced alcohol consumption and preference as well as locomotorstimulating and rewarding properties of ethanol. In this study, we further examined the contribution of mGluR7 on the effect of ethanol within the nucleus accumbens (NAcc), a neural target for many drugs of abuse. Using short hairpin RNA (shRNA)-expressing lentiviral vectors (LV) to alter locally the activity of mGluR7 in male rats, we have shown that blocking mGluR7 expression increased ethanol consumption and preference in a two-bottle choice drinking paradigm with no effect either on saccharin or on quinine used for taste discrimination. In addition, mGluR7 knockdown increases preference for environments previously paired with low doses of ethanol in the conditioned place preference (CPP) test, as it shifted the dose-response curve for ethanol CPP to the left, indicating alterations in the rewarding effects of alcohol. More importantly, mGluR7 blockade in the dorsal striatum (DS) neither affected ethanol consumption nor ethanol-elicited CPP. These results show that levels of mGluR7 in the NAcc regulate responsiveness to alcohol. Taken together, these findings clearly demonstrate that mGluR7 signaling within the NAcc is a key modulator of functional responses to ethanol and offer an important target for regulating the addictive effects of alcohol.

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Cocaine dependence: a disease of the brain’s reward centers

Cited by 274 publications

References 22 publications

Associations of substance use patterns with attempted suicide among persons who inject drugs: Can distinct use patterns play a role?

Associations of substance use patterns with attempted suicide among persons who inject drugs: Can distinct use patterns play a role?

The evidence for a neurobiological model of childhood antisocial behavior.

Viral-Mediated Knockdown of mGluR7 in the Nucleus Accumbens Mediates Excessive Alcohol Drinking and Increased Ethanol-Elicited Conditioned Place Preference in Rats

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