The effect of nicotine induced behavioral sensitization on dopamine D1 receptor pharmacology: An in vivo and ex vivo study in the rat

Abstract Background Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression. Methods μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels. Results In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages. Conclusion In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.

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Insight into Glutamatergic Involvement in Rewarding Effects of Mephedrone in Rats: In Vivo and Ex Vivo Study

Molecular Neurobiology ◽

10.1007/s12035-021-02404-y ◽

2021 ◽

Author(s):

Olga Wronikowska ◽

Maria Zykubek ◽

Agnieszka Michalak ◽

Anna Pankowska ◽

Paulina Kozioł ◽

...

Keyword(s):

Ex Vivo ◽

Interdisciplinary Approach ◽

Nmda Antagonist ◽

Exchange Chromatography ◽

Resonance Spectroscopy ◽

Monoamine Transporters ◽

Ex Vivo Study ◽

Insight Into

AbstractMephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.

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In vivo andin vitro ethanol exposure in prenatal rat brain: GABAB receptor modulation on dopamine D1 receptor and protein kinase A

Synapse ◽

10.1002/syn.20522 ◽

2008 ◽

Vol 62 (7) ◽

pp. 534-543 ◽

Cited By ~ 13

Author(s):

H.Y. Lee ◽

N. Naha ◽

S.P. Li ◽

M.J. Jo ◽

M.L. Naseer ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinase A ◽

Rat Brain ◽

Gabab Receptor ◽

Ethanol Exposure ◽

Dopamine D1 Receptor ◽

D1 Receptor ◽

Receptor Modulation ◽

Kinase A

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Methylene Blue Staining of Dysplastic and Nondysplastic Barrett's Esophagus: An In Vivo and Ex Vivo Study

Endoscopy ◽

10.1055/s-2001-14427 ◽

2001 ◽

Vol 33 (5) ◽

pp. 391-400 ◽

Cited By ~ 103

Author(s):

M. I. Canto ◽

S. Setrakian ◽

J. E. Willis ◽

A. Chak ◽

R. E. Petras ◽

...

Keyword(s):

Methylene Blue ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Ex Vivo ◽

Blue Staining ◽

Ex Vivo Study

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Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens.

10.1101/2022.01.12.476057 ◽

2022 ◽

Author(s):

Bridget A Matikainen-Ankney ◽

Alex A Legaria ◽

Yvan M Vachez ◽

Caitlin A Murphy ◽

Yiyan A Pan ◽

...

Keyword(s):

Nucleus Accumbens ◽

Food Reward ◽

Ex Vivo ◽

D1 Receptor ◽

Physical Work ◽

Projection Neurons ◽

Food Motivation ◽

Obese Mice ◽

Food Seeking

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with both in vivo electrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. With ex vivo slice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPN activity in obese mice. Finally, blocking synaptic transmission from D1SPNs decreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNs during food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNs in the development of diet-induced obesity, identifying a novel potential therapeutic target.

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