Effect of chronic cocaine on dopamine synthesis in the nucleus accumbens as determined by microdialysis perfusion with NSD-1015

Brock, JW; Ng, JP; Justice, Jr Jb

doi:10.1016/0304-3940(90)90150-8

Cited by 42 publications

(25 citation statements)

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“…Repeated cocaine administration increases dopamine release in NAcc (Weiss et al, ). This enhancement of dopamine signaling has shown to increase D 1 dopamine receptor sensitivity for up to several weeks in NAcc (Henry and White, ), which in turn could trigger compensatory mechanisms, such as a decreased synthesis of DA (Brock et al, ) by reducing TH activity and/or expression. The disruption of axonal transport of TH from the VTA to the NAcc could also account for the reduced TH expression observed after repeated cocaine administration (Beitner‐Johnson et al, ).…”

Section: Discussionmentioning

confidence: 99%

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Galeano

Romero

Rojas

et al. 2013

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Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction.

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Section: Discussionmentioning

confidence: 99%

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Galeano

Romero

Rojas

et al. 2013

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“…We previously found reduced TH levels in the NAc of rats self-administering heroin , and others have found TH deficits in the NAc following chronic ethanol self-administration (Ortiz et al 1995). Thus, chronic self-administration of a variety of addictive drugs reduces the amount of TH in the NAc, and could contribute to reduced dopamine synthesis and basal extracellular levels in withdrawal from chronic drug administration (Brock et al 1990;Pothos et al 1991;Rossetti et al 1992;Weiss et al 1992;Diana et al 1993).…”

Section: Results and Discussion Extinction Training Reverses Cocaine-mentioning

confidence: 99%

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Self¹,

Choi²,

Simmons³

et al. 2004

Learn. Mem.

114

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Cocaine produces multiple neuroadaptations with chronic repeated use. Many of these neuroadaptations can be reversed or normalized by extinction training during withdrawal from chronic cocaine self-administration in rats. This article reviews our past and present studies on extinction-induced modulation of the neuroadaptive response to chronic cocaine in the mesolimbic dopamine system, and the role of this modulation in addictive behavior in rats. Extinction training normalizes tyrosine hydroxylase levels in the nucleus accumbens (NAc) shell, an effect that could help ameliorate dysphoria and depression associated with withdrawal from chronic cocaine use. Extinction training also increases levels of GluR1 and GluR2/3 AMPA receptor subunits, while normalizing deficits in NR1 NMDA receptor subunits, in a manner consistent with long-term potentiation of excitatory synapses in the NAc shell. Our results suggest that extinction-induced increases in AMPA and NMDA receptors may restore deficits in cortico-accumbal neurotransmission in the NAc shell and facilitate inhibitory control over cocaine-seeking behavior. Other changes identified by gene expression profiling, including up-regulation in the AMPA receptor aggregating protein Narp, suggest that extinction training induces extensive synaptic reorganization. These studies highlight potential benefits for extinction training procedures in the treatment of drug addiction.

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“…Since dephosphorylation of TH decreases its catalytic activity, the morphine-and cocaine-induced decrease in TH phosphorylation in the NAc is probably associated with decreased enzyme activity in this brain region. Indeed, this observed dephosphorylation of TH could account for the reduced levels of in vivo dopamine synthesis observed in response to chronic cocaine administration in the NAc (Brock et al, 1990) and for reduced in vivo levels of basal and morphine-stimulated dopamine release in the NAc in response to chronic administration of morphine (Acquas et al, 1991). As TH present in the NAc is located within dopaminergic nerve terminals of axons projected from the VTA, the results indicate that this enzyme can be regulated by morphine and cocaine differentially in cell body and nerve terminal regions of the mesolimbic dopamine system.…”

Section: Molecularmentioning

confidence: 98%

Molecular mechanisms of drug addiction [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

Ej¹

1992

J. Neurosci.

470

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Drug addiction has afflicted mankind for centuries, yet the mechanisms by which particular drugs lead to addiction, and the genetic factors that make some individuals particularly vulnerable to addiction, have remained elusive. From a clinical perspective, drug abuse continues to exact enormous human and financial costs on society, yet all currently available treatments for drug addiction are notoriously ineffective. The search for a better understanding of the neurobiological mechanisms underlying the addictive actions of drugs of abuse and of the genetic factors that contribute to addiction should be given a high priority, as this should result in crucial advances in our ability to treat and prevent drug addiction.From the basic neuroscience perspective, study of the neurobiology of drug addiction offers a novei opportunity to establish the biological basis of a complex and clinically relevant behavioral abnormality. Many prominent aspects of drug addiction in people can be clearly reproduced in laboratory animals, in striking contrast to most other forms of neuropsychiatric illness, such as psychotic and affective disorders, animal models for which are much harder to interpret. Advances made in the study of drug addiction should provide important insights into mechanisms underlying some of these other disorders.Three terms related to drug abuse are used commonly: tolerance, dependence, and addiction. Tolerance represents a reduced effect upon repeated exposure to a drug at a constant dose, or the need for an increased dose to maintain the same effect. Dependence is defined as the need for continued exposure to a drug so as to avoid a withdrawal syndrome (physical and/ or psychological disturbances) when the drug is withdrawn. Dependence is considered a priori to result from adaptive changes that develop in body tissues in response to repeated drug exposure. The traditional distinction between physical and psychological dependence is somewhat artificial, since both are mediated by neural mechanisms, possibly even similar neural mechanisms, as will be seen below. Addiction is defined as the compulsive use of a drug despite adverse consequences. In the I thank Drs.

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Effect of chronic cocaine on dopamine synthesis in the nucleus accumbens as determined by microdialysis perfusion with NSD-1015

Cited by 42 publications

References 5 publications

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats

Extinction Training Regulates Neuroadaptive Responses to Withdrawal from Chronic Cocaine Self-Administration

Molecular mechanisms of drug addiction [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

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