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Effects of Dopamine D2-Like Receptor Antagonists on Light Responses of Ganglion Cells in Wild-Type and P23H Rat Retinas.

Jensen R - PLoS ONE (2015)

Bottom Line: In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs.Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells.Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

View Article: PubMed Central - PubMed

Affiliation: VA Boston Healthcare System, Mail Stop 151E, 150 South Huntington Avenue, Boston, Massachusetts 02130, United States of America.

ABSTRACT
In animal models of retinitis pigmentosa the dopaminergic system in the retina appears to be dysfunctional, which may contribute to the debilitated sight experienced by retinitis pigmentosa patients. Since dopamine D2-like receptors are known to modulate the activity of dopaminergic neurons, I examined the effects of dopamine D2-like receptor antagonists on the light responses of retinal ganglion cells (RGCs) in the P23H rat model of retinitis pigmentosa. Extracellular electrical recordings were made from RGCs in isolated transgenic P23H rat retinas and wild-type Sprague-Dawley rat retinas. Intensity-response curves to flashes of light were evaluated prior to and during bath application of a dopamine D2-like receptor antagonist. The dopamine D2/D3 receptor antagonists sulpiride and eticlopride and the D4 receptor antagonist L-745,870 increased light sensitivity of P23H rat RGCs but decreased light sensitivity in Sprague-Dawley rat RGCs. In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs. I describe for the first time ON-center RGCs in P23H rats that exhibit an abnormally long-latency (>200 ms) response to the onset of a small spot of light. Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells. Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

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Effects of dopamine D2/D3 receptor antagonists on intensity-response curves of Sprague-Dawley rat RGCs.(A) Intensity-response curve from an ON-center Sprague-Dawley rat RGC to a small spot of light, taken before and during application of sulpiride (10 μM) to the bathing solution. The abscissa is labeled as log-unit attenuation in stimulus intensity from the maximum (8.5 x 1017 photons/cm2/s). Summary data illustrating the change induced by dopamine D2/D3 receptor antagonists in (B) light sensitivity, (C) maximum peak response, and (D) dynamic range of Sprague-Dawley rat RGCs (n = 11). Histogram data are expressed as the mean (SD). Asterisk indicates significantly different from control (P < 0.05).
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pone.0146154.g001: Effects of dopamine D2/D3 receptor antagonists on intensity-response curves of Sprague-Dawley rat RGCs.(A) Intensity-response curve from an ON-center Sprague-Dawley rat RGC to a small spot of light, taken before and during application of sulpiride (10 μM) to the bathing solution. The abscissa is labeled as log-unit attenuation in stimulus intensity from the maximum (8.5 x 1017 photons/cm2/s). Summary data illustrating the change induced by dopamine D2/D3 receptor antagonists in (B) light sensitivity, (C) maximum peak response, and (D) dynamic range of Sprague-Dawley rat RGCs (n = 11). Histogram data are expressed as the mean (SD). Asterisk indicates significantly different from control (P < 0.05).

Mentions: Fig 1A shows the effects of a D2/D3 receptor antagonist on the intensity-response function of a representative Sprague-Dawley rat RGC. The light intensity that evoked a half-maximum response prior to application of sulpiride was –3.50 log units attenuation. With application of sulpiride, the light intensity that evoked the same response was –3.24 log units attenuation. By definition, sulpiride reduced the light sensitivity of the cell by 0.26 log unit. Sulpiride had little effect on either the maximum peak response or the dynamic range (the light intensity span that elicits responses between 10% and 90% of the maximum peak response) of this cell to the spot of light. Fig 1B, 1C and 1D summarize the effects of the D2/D3 receptor antagonists sulpiride and eticlopride on the light sensitivity, maximum peak response and dynamic range of the RGCs (n = 11). On average, the D2/D3 receptor antagonists decreased light sensitivity of the RGCs by 0.23 log unit (from 3.55 ± 0.40 log to 3.32 log ± 0.41 log units attenuation; P = 0.001). No statistically significant effect was observed in either the maximum peak response (P = 0.664) or the dynamic range (P = 0.117) of the RGCs. Taken together, the data suggest that blocking dopamine D2/D3 receptors in the healthy Sprague-Dawley rat retina simply shifts intensity-response curves of RGCs to the right.


Effects of Dopamine D2-Like Receptor Antagonists on Light Responses of Ganglion Cells in Wild-Type and P23H Rat Retinas.

Jensen R - PLoS ONE (2015)

Effects of dopamine D2/D3 receptor antagonists on intensity-response curves of Sprague-Dawley rat RGCs.(A) Intensity-response curve from an ON-center Sprague-Dawley rat RGC to a small spot of light, taken before and during application of sulpiride (10 μM) to the bathing solution. The abscissa is labeled as log-unit attenuation in stimulus intensity from the maximum (8.5 x 1017 photons/cm2/s). Summary data illustrating the change induced by dopamine D2/D3 receptor antagonists in (B) light sensitivity, (C) maximum peak response, and (D) dynamic range of Sprague-Dawley rat RGCs (n = 11). Histogram data are expressed as the mean (SD). Asterisk indicates significantly different from control (P < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4696741&req=5

pone.0146154.g001: Effects of dopamine D2/D3 receptor antagonists on intensity-response curves of Sprague-Dawley rat RGCs.(A) Intensity-response curve from an ON-center Sprague-Dawley rat RGC to a small spot of light, taken before and during application of sulpiride (10 μM) to the bathing solution. The abscissa is labeled as log-unit attenuation in stimulus intensity from the maximum (8.5 x 1017 photons/cm2/s). Summary data illustrating the change induced by dopamine D2/D3 receptor antagonists in (B) light sensitivity, (C) maximum peak response, and (D) dynamic range of Sprague-Dawley rat RGCs (n = 11). Histogram data are expressed as the mean (SD). Asterisk indicates significantly different from control (P < 0.05).
Mentions: Fig 1A shows the effects of a D2/D3 receptor antagonist on the intensity-response function of a representative Sprague-Dawley rat RGC. The light intensity that evoked a half-maximum response prior to application of sulpiride was –3.50 log units attenuation. With application of sulpiride, the light intensity that evoked the same response was –3.24 log units attenuation. By definition, sulpiride reduced the light sensitivity of the cell by 0.26 log unit. Sulpiride had little effect on either the maximum peak response or the dynamic range (the light intensity span that elicits responses between 10% and 90% of the maximum peak response) of this cell to the spot of light. Fig 1B, 1C and 1D summarize the effects of the D2/D3 receptor antagonists sulpiride and eticlopride on the light sensitivity, maximum peak response and dynamic range of the RGCs (n = 11). On average, the D2/D3 receptor antagonists decreased light sensitivity of the RGCs by 0.23 log unit (from 3.55 ± 0.40 log to 3.32 log ± 0.41 log units attenuation; P = 0.001). No statistically significant effect was observed in either the maximum peak response (P = 0.664) or the dynamic range (P = 0.117) of the RGCs. Taken together, the data suggest that blocking dopamine D2/D3 receptors in the healthy Sprague-Dawley rat retina simply shifts intensity-response curves of RGCs to the right.

Bottom Line: In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs.Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells.Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

View Article: PubMed Central - PubMed

Affiliation: VA Boston Healthcare System, Mail Stop 151E, 150 South Huntington Avenue, Boston, Massachusetts 02130, United States of America.

ABSTRACT
In animal models of retinitis pigmentosa the dopaminergic system in the retina appears to be dysfunctional, which may contribute to the debilitated sight experienced by retinitis pigmentosa patients. Since dopamine D2-like receptors are known to modulate the activity of dopaminergic neurons, I examined the effects of dopamine D2-like receptor antagonists on the light responses of retinal ganglion cells (RGCs) in the P23H rat model of retinitis pigmentosa. Extracellular electrical recordings were made from RGCs in isolated transgenic P23H rat retinas and wild-type Sprague-Dawley rat retinas. Intensity-response curves to flashes of light were evaluated prior to and during bath application of a dopamine D2-like receptor antagonist. The dopamine D2/D3 receptor antagonists sulpiride and eticlopride and the D4 receptor antagonist L-745,870 increased light sensitivity of P23H rat RGCs but decreased light sensitivity in Sprague-Dawley rat RGCs. In addition, L-745,870, but not sulpiride or eticlopride, reduced the maximum peak responses of Sprague-Dawley rat RGCs. I describe for the first time ON-center RGCs in P23H rats that exhibit an abnormally long-latency (>200 ms) response to the onset of a small spot of light. Both sulpiride and eticlopride, but not L-745,870, reduced this ON response and brought out a short-latency OFF response, suggesting that these cells are in actuality OFF-center cells. Overall, the results show that the altered dopaminergic system in degenerate retinas contributes to the deteriorated light responses of RGCs.

Show MeSH
Related in: MedlinePlus