Role Of Dopamine In Addiction Research Articles

Dopamine and addiction: what have we learned from 40years of research.

Among the neurotransmitters involved in addiction, dopamine (DA) is clearly the best known. The critical role of DA in addiction is supported by converging evidence that has been accumulated in the last 40 years. In the present review, first we describe the dopaminergic system in terms of connectivity, functioning and involvement in reward processes. Second, we describe the functional, structural, and molecular changes induced by drugs within the DA system in terms of neuronal activity, synaptic plasticity and transcriptional and molecular adaptations. Third, we describe how genetic mouse models have helped characterizing the role of DA in addiction. Fourth, we describe the involvement of the DA system in the vulnerability to addiction and the interesting case of addiction DA replacement therapy in Parkinson's disease. Finally, we describe how the DA system has been targeted to treat patients suffering from addiction and the result obtained in clinical settings and we discuss how these different lines of evidence have been instrumental in shaping our understanding of the physiopathology of drug addiction.

Misuse and Associated Harms of Quetiapine and Other Atypical Antipsychotics.

Recent years have seen a significant increase in the reports of atypical antipsychotic diversion, misuse and even dependency syndrome. These reports have arisen amidst a marked increase in prescribing of these agents. Much of this increase in prescribing is because of a preferential use of these medications over typical antipsychotic agents to treat schizophrenia and bipolar disorder due to perceptions of fewer extrapyramidal side effects. However, there has also been a significant increase in the off-label prescribing of these medicines to treat less well evidence-based conditions. Misuse and abuse are perhaps surprising given the putative central role of dopamine in addiction and that these agents are dopamine antagonists. However, there may be other factors such as other pharmacological effects and increasing availability driving this misuse. It is also apparent that certain patient groups appear to be more at risk. Here, we explore the evidence behind the misuse of atypical antipsychotics with a focus of quetiapine. We consider the factors that may be driving this misuse, and then, we also detail some of the adverse effects that may ensue. We end by suggesting interventions at a prescriber and systems level that may be implemented to reduce the risk of atypical antipsychotic misuse.

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction remains unclear. Positron emission tomography (PET) is the first technology used for in vivo measurement of components of the dopaminergic system in the human brain. In this article, we review the major findings from PET imaging studies on the involvement of DA in drug addiction, including presynaptic DA synthesis, vesicular monoamine transporter 2, the DA transporter, and postsynaptic DA receptors. These results have corroborated the role of DA in addiction and increased the understanding of its underlying mechanisms.

Altered Ratio of D1 and D2 Dopamine Receptors in Mouse Striatum Is Associated with Behavioral Sensitization to Cocaine

BackgroundDrugs of abuse elevate brain dopamine levels, and, in vivo, chronic drug use is accompanied by a selective decrease in dopamine D2 receptor (D2R) availability in the brain. Such a decrease consequently alters the ratio of D1R∶D2R signaling towards the D1R. Despite a plethora of behavioral studies dedicated to the understanding of the role of dopamine in addiction, a molecular mechanism responsible for the downregulation of the D2R, in vivo, in response to chronic drug use has yet to be identified.Methods and FindingsEthics statement: All animal work was approved by the Gallo Center IACUC committee and was performed in our AAALAC approved facility. In this study, we used wild type (WT) and G protein coupled receptor associated sorting protein-1 (GASP-1) knock out (KO) mice to assess molecular changes that accompany cocaine sensitization. Here, we show that downregulation of D2Rs or upregulation of D1Rs is associated with a sensitized locomotor response to an acute injection of cocaine. Furthermore, we demonstrate that disruption of GASP-1, that targets D2Rs for degradation after endocytosis, prevents cocaine-induced downregulation of D2Rs. As a consequence, mice with a GASP-1 disruption show a reduction in the sensitized locomotor response to cocaine.ConclusionsTogether, our data suggests that changes in the ratio of the D1R∶D2R could contribute to cocaine-induced behavioral plasticity and demonstrates a role of GASP-1 in regulating both the levels of the D2R and cocaine sensitization.

The Neurobiology of Addiction: Where We Have Been and Where We Are Going.

A number of dramatic breakthroughs in the neurobiology of addiction have occurred in the past 40 years. Two domains will be highlighted: the neurocircuitry of addiction and the molecular biology of addiction targets. The neurobiological substrates for the reinforcing effects of drugs of abuse have been largely identified both at the initial site of action and in the circuitry involved. In human imaging studies, decreases in dopaminergic function have been identified as a key element of addiction, lending support for research on the role of dopamine in addiction. Three novel areas currently are emerging: the role of deficits in frontal cortex functioning, changes in the brain neurocircuitry that convey long-term vulnerability to relapse, and the role of nondopaminergic systems in the neuroadaptations associated with the development of drug dependence. Parallel to these functional changes have been major advances in our understanding of the molecular biology of addiction; the greatest contribution has been in the understanding of the molecular mechanisms of opioid action. This paper reviews the major developments in our understanding of the molecular biology of the endogenous opioid system and the use of genomics to advance our knowledge of the function and regulation of opioid receptors and endorphins.