Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors
- Oregon Health & Science University, United States
- University of California, Irvine, United States
- VA Portland Health Care System, United States
Figures
Figure 1
Cocaine-induced adaptation in D2 receptor desensitization.
Shown on the left are representative traces from naïve and cocaine-treated groups in all genotypes of quinpirole (quin., 10 µM)-induced D2 receptor-GIRK currents (I-quinpirole) reversed by sulpiride (sulp., 600 nM) recorded from dopamine neurons in the SNc using EGTA internal solution. For further comparison, scaled and peak aligned current declines are also shown (horizontal scale bars = 90 s, vertical scale bars = 100 pA). (A) In wild type animals there were significant overall effects of internal solution (F(1, 30)=23.57, p<0.001) and cocaine treatment (20 mg/kg, F(1, 30)=4.259, p=0.048) on the decline of I-quinpirole. Post-hoc analyses indicate that in both treatment conditions the decline using BAPTA (B) internal was less than that using EGTA (E, p<0.001 for naïve and coc-treated). Additionally, with EGTA internal there was significantly reduced decline following cocaine treatment (p=0.049, n = 7–9 neurons from 5 to 8 mice). (B) In mice in which the long isoform of the D2 receptor has been knocked out (D2L-KO), there was an overall effect of internal solution (F(1, 32)=37.09, p<0.001), but not of cocaine treatment (F (1, 32)=2.917, p=0.097). In post hoc analyses, there was significantly more decline when using EGTA internal than BAPTA internal in both treatment conditions (p<0.001 for naïve, p=0.002 for cocaine-treated), and the decline was significantly reduced following drug exposure when EGTA internal was used (p=0.021, n = 8–12 neurons from 4 to 7 mice). (C) In animals with the short isoform of the D2 receptor knocked out (D2S-KO), there was an overall effect of internal solution (F(1, 28)=21.24, p<0.001) with EGTA currents declining significantly more that those of BAPTA in both treatment conditions (p=0.001 for naïve, p=0.007 for coc-treated, n = 7–9 neurons from 4 to 7 mice). Cocaine treatment caused no change in desensitization of the D2-GIRK current in this genotype. Comparisons were done using two-way ANOVAs followed by Fisher’s LSD when p<0.05. *p<0.05, **p<0.01, ***p<0.001.
-
Figure 1—source data 1
- https://doi.org/10.7554/eLife.31924.003
Figure 2
Amplitude of D2-GIRK currents.
(A) In wild type mice, there was an overall significant effect of internal solution on D2-GIRK current density (pA/pF, F(1, 30)=76.32, p<0.001). The current density was greater when using the strong calcium buffering BAPTA (B) internal solution compared with the weak buffering EGTA (E) internal solution (p<0.001 for naïve and coc-treated, n = 7–11 neurons from 5 to 7 mice). There was no difference between naïve and cocaine-treated groups. (B) From D2L-KO mice, there was an overall significant effect of internal solution (F(1, 32)=12.85, p=0.001). The current density of the BAPTA group was significantly larger than that of EGTA in both naïve and coc-treated conditions (p=0.016 for naïve, p=0.016 for coc-treated, n = 7–12 neurons from 4 to 7 mice), however there was no difference between treatment conditions. (C) In D2S-KO mice, there was no significant effect of internal solution or drug treatment (n = 7–9 neurons from 5 to 7 mice). Analyses were done by two-way ANOVAs followed by Fisher’s LSD when p<0.05. *p<0.05, **p<0.01, ***p<0.001.
-
Figure 2—source data 1
- https://doi.org/10.7554/eLife.31924.005
Figure 3
No change in GABAB desensitization following cocaine exposure.
GABAB receptor decline/desensitization was measured by bath application of baclofen (30 µM) for ~5 min. There were no significant effects of EGTA (E, 0.01 mM) versus BAPTA (B, 10 mM) internal solution or treatment condition (naïve versus coc-treated) on the decline in GABAB-GIRK currents (I-baclofen) from (A) wild type mice, (B) D2L-KO mice, or (C) D2S-KO mice (p<0.05, n = 5–9 neurons from 3 to 6 mice). Analyses were done using two-way ANOVAs.
-
Figure 3—source data 1
- https://doi.org/10.7554/eLife.31924.007
Additional files
-
Transparent reporting form
- https://doi.org/10.7554/eLife.31924.008
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors
eLife 6:e31924.
https://doi.org/10.7554/eLife.31924
