Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration

Schwarz, Adam J.; Zocchi, Alessandro; Reese, Torsten; Gozzi, Alessandro; Garzotti, Marco; Varnier, Giorgia; Curcuruto, Ornella; Sartori, Ilaria; Girlanda, Elena; Biscaro, Barbara; Crestan, Valerio; Bertani, Simone; Heidbreder, Christian; Bifone, Angelo

doi:10.1016/j.neuroimage.2004.05.001

Cited by 64 publications

(48 citation statements)

References 35 publications

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“…Since AMPH not only occupies (and blocks) the DAT binding site (similar to cocaine or MPH), but also enhances DA efflux, the dose of AMPH we used leads to much greater synaptic DA concentrations than similar doses of cocaine or MPH [Sulzer et al, 2005]. Microdialysis studies in adult rats using pharmacological doses similar to our study found the degree of DA efflux is: AMPH 1 1,000%, cocaine ϳ 300%, MPH ϳ 450% of the baseline level [Butcher et al, 1991;Feigenbaum and Howard, 1997;Ito et al, 2002;Porras et al, 2003;Schwarz et al, 2004]. The extra amount of DA released by AMPH increases the likelihood of D1R binding, and is reflected in the rCBV increase in the young rats.…”

Section: Discussionsupporting

confidence: 71%

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Chen

Choi

et al. 2010

Dev Neurosci

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Characterization of the ontogeny of the cerebral dopaminergic system is crucial for gaining a greater understanding of normal brain development and its alterations in response to drugs of abuse or conditions such as attention-deficit hyperactivity disorder. Pharmacological MRI (phMRI) was used to determine the response to dopamine transporter (DAT) blockers cocaine and methylphenidate (MPH), the dopamine releaser D-amphetamine (AMPH), the selective D1 agonist dihydrexidine, and the D2/D3 agonist quinpirole in young (<30 days old) and adult (>60 days old) rats. In adult rats, cocaine (0.5 mg/kg i.v.) or MPH (2 mg/kg) induced primarily positive cerebral blood volume (rCBV) changes in the dopaminergic circuitry, but negative rCBV changes in the young animals. Microdialysis measurements in the striatum showed that young rats have a smaller increase in extracellular dopamine in response to cocaine than adults. The young rats showed little rCBV response to the selective D1 agonist dihydrexidine in contrast to robust rCBV increases observed in the adults, whereas there was a similar negative rCBV response in the young and adult rats to the D2 agonist quinpirole. We also performed a meta-analysis of literature data on the development of D1 and D2 receptors and the DAT. These data suggest a predominance of D2-like over D1-like function between 20 and 30 days of age. These combined results suggested that the dopamine D1 receptor is functionally inhibited at young age.

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Section: Discussionsupporting

confidence: 71%

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Chen

Choi

et al. 2010

Dev Neurosci

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“…Therefore, the findings in our study should also be understood in terms of anatomical circuits where dopaminergic stimulation induces changes in glutamate release in connected anatomical regions. Although previous studies have shown psychostimulant-induced decreases in absolute global blood flow [Kahn et al, 1989;Wallace et al, 1996;Wang et al, 1994], it is unlikely that direct vasoactivity of DA is the dominant mechanism underlying the changes in relative rCBF [Schwarz et al, 2004]. In addition, no deviations in the relationship between local glucose utilization and local blood flow were found after administration of the dopamine agonist apomorphine .…”

Section: Discussionmentioning

confidence: 77%

“…A review of the literature shows that psychostimulant administration does not consistently affect striatal activation. Previous human and animal studies have reported activations [Chen at al., 1997;Dixon et al, 2005;Ernst et al, 1997;Marota et al, 2000;Schwarz et al, 2004], deactivations [Cash et al, 2003;Volkow et al, 1997], or no changes [Howell et al, 2002;Mehta et al, 2000;Vollm et al, 2004] in relative rCBF or brain metabolism. Drug administration also resulted in variable effects on absolute rCBF or metabolism.…”

Section: Discussionmentioning

confidence: 99%

Methylphenidate‐induced activation of the anterior cingulate but not the striatum: A [¹⁵O]H₂O PET study in healthy volunteers

Haes

Maguire

Jager

et al. 2006

Human Brain Mapping

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The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders, such as schizophrenia, depression, and addiction. (Dys)function of the dopaminergic system may be studied by combining [15O]H2O PET with a dopaminergic drug challenge. In this pilot study we investigated the suitability of the dopamine reuptake blocker methylphenidate (MP) as a dopaminergic probe. Measurements of regional cerebral blood flow (rCBF) were made at 10 and 30 min after placebo and MP (0.25 mg/kg) injection to seven healthy volunteers. During scanning the behavioral condition of the subjects was standardized using a continuous performance task. Growth hormone levels were assessed and subjective ratings were obtained. MP significantly elevated growth hormone levels. After receiving MP, the subjective experience varied from neutral to highly pleasurable. Ten minutes after MP administration, significant relative increases in rCBF were found in the rostral anterior cingulate (AC), temporal poles, and the supplementary motor area. Significant reductions were seen in the superior temporal gyri, right medial frontal gyrus, and right inferior parietal cortex. At 30 min after MP administration, increases were seen in the AC, temporal pole, and right cerebellum. No changes were observed in the striatum. The activation in the right rostral AC was significantly higher in the subjects with the highest euphoria scores compared to the subjects with minimal MP-induced changes in euphoria. We suggest that the combined MP challenge with functional imaging, as described in our study, may be a useful tool to study the functional integrity of the dopaminergic system in psychiatric disorders.

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“…Since the advent of phMRI, a number of mechanisms of action and compounds have been evaluated in the preclinical domain. With use of phMRI, drug action on rodent brain function has been evaluated for a range of compounds that include amphetamine (Chen et al, 2005), nicotine (Gozzi et al, 2006), remifentanil (Liu et al, 2007), and cocaine (Schwarz et al, 2004). Previous studies have also used phMRI as a means to characterize the effects of a pharmacological pretreatment (eg, 5HT-2A receptor antagonist) on a particular challenge (e.g., phencylidine) (Gozzi et al, 2008;Gozzi et al, 2010;Chin et al, 2011;Large et al, 2011;McKie et al, 2011;Baker et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy Human Subjects

Becerra

Upadhyay

Chang

et al. 2013

J Pharmacol Exp Ther

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Pharmacological magnetic resonance imaging (phMRI) is one method by which a drug's pharmacodynamic effects in the brain can be assessed. Although phMRI has been frequently used in preclinical and clinical settings, the extent to which a phMRI signature for a compound translates between rodents and humans has not been systematically examined. In the current investigation, we aimed to build on recent clinical work in which the functional response to 0.1 and 0.2 mg/70 kg i.v. buprenorphine (partial m-opioid receptor agonist) was measured in healthy humans. Here, we measured the phMRI response to 0.04 and 0.1 mg/kg i.v. buprenorphine in conscious, naive rats to establish the parallelism of the phMRI signature of buprenorphine across species. PhMRI of 0.04 and 0.1 mg/kg i.v. buprenorphine yielded dose-dependent activation in a brain network composed of the somatosensory cortex, cingulate, insula, striatum, thalamus, periaqueductal gray, and cerebellum. Similar dose-dependent phMRI activation was observed in the human phMRI studies. These observations indicate an overall preservation of pharmacodynamic responses to buprenorphine between conscious, naive rodents and healthy human subjects, particularly in brain regions implicated in pain and analgesia. This investigation further demonstrates the usefulness of phMRI as a translational tool in neuroscience research that can provide mechanistic insight and guide dose selection in drug development.

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Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration

Cited by 64 publications

References 35 publications

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Methylphenidate‐induced activation of the anterior cingulate but not the striatum: A [¹⁵O]H₂O PET study in healthy volunteers

Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy Human Subjects

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Concurrent pharmacological MRI and in situ microdialysis of cocaine reveal a complex relationship between the central hemodynamic response and local dopamine concentration

Cited by 64 publications

References 35 publications

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Pharmacologic Neuroimaging of the Ontogeny of Dopamine Receptor Function

Methylphenidate‐induced activation of the anterior cingulate but not the striatum: A [15O]H2O PET study in healthy volunteers

Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy Human Subjects

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Methylphenidate‐induced activation of the anterior cingulate but not the striatum: A [¹⁵O]H₂O PET study in healthy volunteers