Cortical Dopaminergic Involvement in Cocaine Reinforcement

Goeders, Nicholas E.; Smith, James E.

doi:10.1126/science.6879176

Cited by 465 publications

(181 citation statements)

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“…The current data also fail to provide simple correlations with models that postulate that enhanced PFc DA levels are necessary and sufficient for cocaine reward. This hypothesis has also been supported by a substantial body of lesion and microinjection data (Goeders and Smith, 1983;Goeders et al, 1986;Bardo, 1998;Tzschentke, 2001). Cocaine increases DA ex in PFc of both wild-type and homozygous DAT-KO mice that exhibit cocaine reward and DAT/SERT double homozygous KO mice that do not display cocaine reward.…”

Section: Differential Da Responses In To Cocaine In Cpu Nac and Pfcmentioning

confidence: 74%

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Shen

Hagino

Kobayashi

et al. 2004

Neuropsychopharmacol

184

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Cocaine conditioned place preference (CPP) is intact in dopamine transporter (DAT) knockout (KO) mice and enhanced in serotonin transporter (SERT) KO mice. However, cocaine CPP is eliminated in double-KO mice with no DAT and either no or one SERT gene copy. To help determine mechanisms underlying these effects, we now report examination of baselines and drug-induced changes of extracellular dopamine (DA ex ) and serotonin (5-HT ex ) levels in microdialysates from nucleus accumbens (NAc), caudate putamen (CPu), and prefrontal cortex (PFc) of wild-type, homozygous DAT-or SERT-KO and heterozygous or homozygous DAT/SERT double-KO mice, which are differentially rewarded by cocaine. Cocaine fails to increase DA ex in NAc of DAT-KO mice. By contrast, systemic cocaine enhances DA ex in both CPu and PFc of DAT-KO mice though local cocaine fails to affect DA ex in CPu. Adding SERT to DAT deletion attenuates the cocaine-induced DA ex increases found in CPu, but not those found in PFc. The selective SERT blocker fluoxetine increases DA ex in CPu of DAT-KO mice, while cocaine and the selective DAT blocker GBR12909 increase 5-HT ex in CPu of SERT-KO mice. These data provide evidence that (a) cocaine increases DA ex in PFc independently of DAT and that (b), in the absence of SERT, CPu levels of 5-HT ex can be increased by blocking DAT. Cocaine-induced alterations in CPu DA levels in DAT-, SERT-, and DAT/SERT double-KO mice appear to provide better correlations with cocaine CPP than cocaine-induced DA level alterations in NAc or PFc.

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Section: Differential Da Responses In To Cocaine In Cpu Nac and Pfcmentioning

confidence: 74%

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Shen

Hagino

Kobayashi

et al. 2004

Neuropsychopharmacol

184

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“…ICV CRH has little or no effect on dopamine in the nucleus accumbens (Kalivas et al 1987;Dunn and Berridge 1990) and actually increases dopamine metabolism in the medial prefrontal cortex (Dunn and Berridge 1990). Nevertheless, in consideration of the putative dual role for the medial prefrontal cortex in the neurobiological response to stress as well as in the initiation of cocaine-seeking behavior (Goeders and Smith 1983;Goeders 1997), it is likely that CRHinduced alterations in dopaminergic neurotransmission play an important role in this peptide's effects on cocaine responsiveness.…”

Section: Discussionmentioning

confidence: 99%

Effects of the CRH Receptor Antagonist CP-154,526 on Intravenous Cocaine Self-administration in Rats

Goeders

Guerin

2000

Neuropsychopharmacology

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The role for corticotropin-releasing hormone (CRH) receptors in the maintenance of intravenous cocaine self-administration in rats was investigated using the centrally active, small molecule CRH1 receptor antagonist 526. In these experiments, adult male Wistar rats were allowed alternating 15-min periods of access to food reinforcement and cocaine selfadministration (0.125, 0.25 Self-administration; Rat During the past several years, research from our laboratory has focused on the potential involvement of the hypothalamic-pituitary-adrenal (HPA) axis in cocaine reinforcement. The HPA axis consists of a complex, well-regulated interaction between the brain, the anterior pituitary gland, and the adrenal cortex. The initial step in the activation of the HPA axis is the neuronally regulated secretion of the peptide corticotropin-releasing hormone (CRH) from the parvocellular division of the paraventricular nucleus (PVN) of the hypothalamus. CRH is released by the hypothalamus into the adenohypophyseal portal circulation to act on the pituitary to induce the secretion of adrenocorticotropin hormone (ACTH). ACTH diffuses through the general circulation until it reaches the adrenal glands. There it stimulates the biosynthesis of adrenocorticosteroids, most notably the glucocorticoids, cortisol (in humans) and corticosterone (in rats), which results in their secretion from the adrenal cortex.Cocaine has been reported to stimulate HPA axis activity in a manner analogous to various stressors, which indicates that this system has the potential to influence many of the neurochemical and behavioral effects of the drug. For example, the acute administration of cocaine dose-dependently increases plasma concentrations of corticosterone, ACTH, and ␤ -endorphin in rats (Moldow and Fischman 1987;Rivier and Vale 1987;Borowsky and Kuhn 1991). Cocaine also stimulates the release of ACTH and cortisol in humans (Mendelson et al. 1989;Baumann et al. 1995) and non-human primates (Sarnyai et al. 1996) by increasing the peak amplitude of secretory pulses of these hormones without altering pulse frequency, suggesting that these increases are driven by hypothalamic CRH (Mendelson et al. 1989;Teoh et al. 1994;Sarnyai et al. 1996). Cocaine-induced increases in ACTH and corticosterone in rats can be blocked by pretreatment with the CRH antagonist ␣ -helical CRF 9-41 (Sarnyai et al. 1992a), by immunoneutralization of CRH with an anti-CRH antibody (Rivier and Vale 1987;Sarnyai et al. 1992a), or by bilateral electrolytic lesions of the PVN (Rivier and Lee 1994), indicating that these increases are also mediated by the cocaine-induced release of CRH from parvocellular neurons in the PVN. Accordingly, it has been reported that cocaine administration also results in increases in hypothalamic CRH mRNA (Zhou et al. 1996;Rivier and Lee 1994) and alters CRH receptor binding measured autoradiographically in various regions of the rat brain (Goeders et al. 1990). These data suggest that the complex relationship between cocaine reinforcement and cort...

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“…Self-administration studies have identi®ed cocaine as an extremely powerful reinforcer. Additionally, a substantial body of evidence has linked cocaine's reinforcing properties to its ability to increase dopaminergic neurotransmission within the mesocorticolimbic circuit (Goeders and Smith, 1983). Studies with dopamine receptor agonists and antagonists have demonstrated involvement of both D 1 and D 2 dopamine receptor subtypes in the acute reinforcing effects of cocaine (Bergman et al, 1990).…”

Section: Receptors Mediate Cocaine-induced Behaviorsmentioning

confidence: 99%

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

Hummel

Unterwald

2002

Journal Cellular Physiology

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Cocaine is one of the most abused psychostimulants known to man and as such, researchers have been steadfast in their attempts to understand the neurobiological mechanisms responsible for its abuse. Cocaine undoubtedly wreaks havoc on a number of mammalian neuronal neurotransmitter systems, and it is maintained that this dysregulatory effect supports cocaine abuse. Cocaine's mechanism of action has been well described. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the reuptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons (Heikkila et al., 1975, Biochem Pharmacol 24(8):847±852;Reith et al., 1986, Biochem Pharmacol 35(7):1123±1129; Ritz et al., 1987, Science 237:1219± 1223. Inhibition of re-uptake subsequently elevates the synaptic concentrations of each of these neurotransmitters. In addition to this direct effect, cocaine also produces a number of indirect actions, which alter other neuromodulatory systems (i.e., opioidergic, glutamatergic, and GABAergic systems). Many of these effects are just beginning to be elucidated, but nonetheless contribute to this agent's diverse pharmacological pro®le. Interestingly, it is the indirect actions of this melli¯uous molecule, which mediate most of its sought and unsought effects. The intricacy with which cocaine produces neuronal alterations beyond its direct effects on neurotransmitter re-uptake appear to be most relevant to cocaine abuse, and hence the phenomenon of addiction. In light of cocaine's multifarious effects on numerous neuronal systems, its effect on dopaminergic neurotransmission has attracted the most attention, particularly because of the implicated role of dopamine in brain reward. Pharmacologically, the psychostimulant effects of cocaine appear to be mediated by its ability to enhance dopaminergic activity within the mesocorticolimbic circuit (Roberts et al., 1977, Pharmacol Biochem Behav 6(6):615±620). Additionally, it is the intensity with which cocaine produces alterations in dopaminergic circuitry that have enabled this drug to prevail as one of the most addictive substances known to man. This review will summarize ®ndings relevant to cocaine-induced alterations in dopaminemediated signal transduction. Speci®cally, it will concentrate on the D 1 dopamine receptor and intracellular signaling mediated by this receptor subtype. It will describe cocaine-induced cellular and behavioral alterations relevant to this pathway and how these changes potentially effect gene transcription and protein expression. This article too will review a common behavioral manifestation associated with repeated cocaine exposure, sensitization, and why the D 1 dopamine receptor and its associated signaling pathway have been implicated in this phenomenon. Lastly, this article will discuss how targeting the D 1 dopamine receptor and its signaling pathway may offer some insight into understanding cocaine addiction, a somewhat elusive brain disease.

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Cortical Dopaminergic Involvement in Cocaine Reinforcement

Cited by 465 publications

References 17 publications

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Effects of the CRH Receptor Antagonist CP-154,526 on Intravenous Cocaine Self-administration in Rats

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action

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Cortical Dopaminergic Involvement in Cocaine Reinforcement

Cited by 465 publications

References 17 publications

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters

Effects of the CRH Receptor Antagonist CP-154,526 on Intravenous Cocaine Self-administration in Rats

D1 dopamine receptor: A putative neurochemical and behavioral link to cocaine action

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Product

Resources

About

D₁ dopamine receptor: A putative neurochemical and behavioral link to cocaine action