scholarly journals Effects of Environmental Enrichment on Nicotine Sensitization in Rats Neonatally Treated with Quinpirole: Analyses of Glial Cell Line-Derived Neurotrophic Factor and Implications towards Schizophrenia

2018 ◽  
Vol 40 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Russell W. Brown ◽  
Marjorie A. Schlitt ◽  
Alex S. Owens ◽  
Caitlynn C. DePreter ◽  
Elizabeth D. Cummins ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neural Plasticity ◽  
Neurotrophic Factor ◽  
Environmental Enrichment ◽  
Behavioral Sensitization ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Housing Condition ◽  
Dopamine D2

The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal’s lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment. Rats were behaviorally sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38 to P45, and brain tissue was harvested at P46. Results revealed that neither housing condition reduced nicotine sensitization in NQ rats, whereas enrichment reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a neurotrophin important in dopamine plasticity. Results were complex, and revealed that NAcc GDNF was increased in animals given nicotine, regardless of housing condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent drug treatment and in NS-treated rats given nicotine, but did not increase GDNF in NS-treated controls compared to the isolated housing condition. This study demonstrates that environmental experience has a prominent impact on the behavioral and the neural plasticity NAcc response to nicotine in adolescence.

scholarly journals Ciliary Neurotrophic Factor Mediates Dopamine D2 Receptor-Induced CNS Neurogenesis in Adult Mice

2008 ◽  
Vol 28 (9) ◽  
pp. 2231-2241 ◽  
Author(s):  
P. Yang ◽  
S. A. Arnold ◽  
A. Habas ◽  
M. Hetman ◽  
T. Hagg
Keyword(s):  
Neurotrophic Factor ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Ciliary Neurotrophic Factor ◽  
Dopamine D2 ◽  
Adult Mice

Neonatal co-lesion by DSP-4 and 5,7-DHT produces adulthood behavioral sensitization to dopamine D2 receptor agonists

2009 ◽  
Vol 61 (2) ◽  
pp. 311-318 ◽  
Author(s):  
Przemysław Nowak ◽  
Dariusz Nitka ◽  
Adam Kwieciński ◽  
Jadwiga Jośko ◽  
Jacek Drab ◽  
...  
Keyword(s):  
Behavioral Sensitization ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Receptor Agonists ◽  
Dopamine D2

scholarly journals The Dopamine D2 Receptor Contributes to the Spheroid Formation Behavior of U87 Glioblastoma Cells

Pharmacology ◽  
2019 ◽  
Vol 105 (1-2) ◽  
pp. 19-27 ◽  
Author(s):  
Jillian S. Weissenrieder ◽  
Jessie L. Reed ◽  
Michelle V. Green ◽  
George-Lucian Moldovan ◽  
Emily J. Koubek ◽  
...  
Keyword(s):  
Cell Line ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Continuous Treatment ◽  
Spheroid Formation ◽  
Cell Frequency ◽  
Dopamine D2 ◽  
The Impact

Background: Glioblastoma multiforme (GBM) is a common and lethal cancer of the central nervous system. This cancer is difficult to treat because most anticancer therapeutics do not readily penetrate into the brain due to the tight control at the cerebrovascular barrier. Numerous studies have suggested that dopamine D2 receptor (D2R) antagonists, such as first generation antipsychotics, may have anticancer efficacy in vivo and in vitro. The role of the D2R itself in the anticancer effects is unclear, but there is evidence suggesting that D2R activation promotes stem-like and spheroid forming behaviors in GBM. Objectives: We aimed to observe the role of the dopamine D2R and its modulators (at selective concentrations) in spheroid formation and stemness of GBM cell line, U87MG, to clarify the validity of the D2R as a therapeutic target for cancer therapy. Methods: Spheroid formation assays and Western blotting of the glioblastoma cell line, U87MG, were used to observe responses to treatment with the D2R agonists sumanirole, ropinirole, and 4-propyl-9-hydroxynaphthoxazine (PHNO); and the D2R antagonists thioridazine, pimozide, haloperidol, and remoxipride. Extreme limiting dilution analysis was done to determine the impact of sumanirole and remoxipride treatment on sphere-forming cell frequency. Proliferation was also measured by crystal violet staining. Stable lentiviral transduction of DRD2 or shDRD2 was used to validate the role of the D2R in assay behaviors. Results: D2R antagonists thioridazine, pimozide, haloperidol, and remoxipride decrease spheroid formation behaviors at a selective 100 nmol/L concentration, while D2R agonists PHNO, sumanirole, and ropinirole increase the formation of spheroids. Similarly, 100 nmol/L remoxipride decreased sphere-forming cell frequency. These results were recapitulated with genetic overexpression and knockdown of the D2R, and combination experiments indicate that the D2R is required for the effects of the pharmacological modulators. Furthermore, spheroid proliferation and invasive capacity increased under treatment with 100 nmol/L sumanirole and decreased under treatment with 100 nmol/L thioridazine. Expression levels of the stemness markers Nestin and Sox2, as well as those of differentiation marker glial fibrillary acidic protein, were not altered by 100 nmol/L thioridazine or sumanirole for 72 h or continuous treatment with these compounds for 7 days during a spheroid formation assay. Conclusions: Signaling activity of the dopamine D2R may be involved in the spheroid formation phenotype in the context of the U87MG cell line. However, this modulation may not be due to alterations in stemness marker expression, but due to other factors that may contribute to spheroid formation, such as cell-cell adhesion or EGFR signaling.

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