Could a common biochemical mechanism underlie addictions?

Betz, Cecily Lynn; Mihalic, D.; Pinto, Marie E; Raffa, Robert B.

doi:10.1046/j.1365-2710.2000.00260.x

Cited by 39 publications

(36 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is evidence suggesting substantial genetic and environmental nonspecificity across addictive behaviors. 8,16,17 For example, genetic studies reveal common molecular mechanisms for drug addiction and compulsive running behavior. [18][19][20] Similarly, pathological gambling shares a common genetic vulnerability with alcohol dependence.…”

Section: Shared Neurobiological Antecedentsmentioning

confidence: 99%

Toward a Syndrome Model of Addiction: Multiple Expressions, Common Etiology

Shaffer

LaPlante²,

LaBrie³

et al. 2004

Harvard Review of Psychiatry

563

381

View full text Add to dashboard Cite

The important thing in science is not so much to obtain new facts as to discover new ways of thinking about them" Sir William Bragg (1862Bragg ( -1942 It is common for clinicians, researchers, and public policymakers to describe certain drugs or objects (e.g., games of chance) as "addictive," tacitly implying that the cause of addiction resides in the properties of drugs or other objects. Conventional wisdom encourages this view by treating different excessive behaviors, such as alcohol dependence and pathological gambling, as distinct disorders. Evidence supporting a broader conceptualization of addiction is emerging. For example, neurobiological research suggests that addictive disorders might not be independent: 2 each outwardly unique addiction disorder might be a distinctive expression of the same underlying addiction syndrome. Recent research pertaining to excessive eating, gambling, sexual behaviors, and shopping also suggests that the existing focus on addictive substances does not adequately capture the origin, nature, and processes of addiction. The current view of separate addictions is similar to the view espoused during the early days of AIDS diagnosis, when rare diseases were not yet recognized as opportunistic infections of an underlying immune deficiency syndrome. Our analysis of the extant literature reveals that the specific objects of addiction play a less central role in the development of addiction than previously thought, and it identifies the need for a more comprehensive philosophy of addiction.In this article, we suggest that evidence of multiple and interacting biopsychosocial antecedents, manifestations, and consequents-within and among behavioral and substance-related patterns of excess-reflects an underlying addiction syndrome. We propose, in particular, that addiction should be understood as a syndrome with multiple opportunistic expressions (e.g., substance use disorders and pathological gambling). Our goals in this column are to (1) describe a new, syndromal model of addiction, (2) review the most recent literature that supports viewing addiction as a syndrome, and (3) indicate how this perspective can advance clinical practice and identify areas in which more research is needed. To accomplish these goals, we review the empirical evidence for this addiction syndrome and organize it into three primary areas: (1) shared neurobiological antecedents, (2) shared psychosocial antecedents, and (3) shared experiences (e.g., manifestations and sequelae).

show abstract

Section: Shared Neurobiological Antecedentsmentioning

confidence: 99%

Toward a Syndrome Model of Addiction: Multiple Expressions, Common Etiology

Shaffer

LaPlante²,

LaBrie³

et al. 2004

Harvard Review of Psychiatry

563

381

View full text Add to dashboard Cite

show abstract

“…Therefore, investigating approachavoidance behavior has attracted increasing attention, particularly in the drug addiction field [4,[8][9][10]. But the detailed mechanisms underlying approach-avoidance behavior are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Yan

Cheng

et al. 2016

Neurosci. Bull.

View full text Add to dashboard Cite

Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4 -/-) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4 -/-mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4 -/-mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approachavoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4 -/-mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4 -/-mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4 -/-mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.

show abstract

“…Family, twin, and adoption studies suggest a genetic component [Tsuang et al, 1996;Crabbe, 2002] with biochemical and genetic evidence for a common neurochemical pathway acting across classes of abused drugs, including cocaine, methamphetamine, and heroin [Betz et al, 2000;Tsuang et al, 2001]. This implies that genetic risk is encoded mainly by central neurochemical pathways related to reinforcement and reward.…”

Section: Introductionmentioning

confidence: 99%

Association analysis of the DRD4 and COMT genes in methamphetamine abuse

Chen

et al. 2004

American J of Med Genetics Pt B

100

View full text Add to dashboard Cite

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.

show abstract

Could a common biochemical mechanism underlie addictions?

Cited by 39 publications

References 83 publications

Toward a Syndrome Model of Addiction: Multiple Expressions, Common Etiology

Toward a Syndrome Model of Addiction: Multiple Expressions, Common Etiology

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict

Association analysis of the DRD4 and COMT genes in methamphetamine abuse

Contact Info

Product

Resources

About