Neuroscience
-
Morphine sensitization is a model of latent, functionally inducible increase in dopamine D(1) receptor-mediated transmission, which may be unmasked by an external stimulus. Morphine-sensitized rats present dopamine D(1) receptor-dependent stereotypies upon morphine challenge and resilience to unavoidable stress-induced behavioral deficits. This tonic increase in dopamine D(1) dopaminergic transmission is counter-adaptive to an enhanced mu-opioid receptor-dependent signaling in striatal areas. ⋯ The stress-induced neurochemical modifications and their sensitivity to receptor antagonists were similar to those observed after acute morphine administration. In conclusion, these results suggest that in the experimental conditions used an increase in dopamine output in striatal areas is followed by a complex neurochemical pattern, in which the initial stimulation of dopamine D(1) receptors triggers a sequence of signaling events that lead to an mGluR(5)-mediated increase in phospho-Thr75 DARPP-32 levels. Since DARPP-32 phosphorylated in Thr75 inhibits cAMP-dependent protein kinase (PKA) activity, the final result is a decrease in the dopamine D(1) receptor-dependent phosphorylation events.
-
Little is known about the G protein-coupled receptor desensitization process during pregnancy. Wistar pregnant rats were treated with (-)N(6)-phenylisopropyladenosine (R-PIA), an adenosine A(1) receptor (A(1)R) agonist, in their drinking water during pregnancy, and the effect on A(1)R/adenylyl cyclase system was studied in both maternal and fetal brain. In maternal brain, binding assays revealed a significant decrease in total receptor numbers in plasma membranes (27%, P<0.05), with no significant changes in receptor affinity. ⋯ On the other hand, forskolin- and forskolin-plus guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S)-stimulated adenylyl cyclase activity was decreased in maternal (P<.01) and fetal brain (P<.001). Furthermore, adenylyl cyclase inhibition elicited by N(6)-cyclohexyladenosine (CHA), a selective A(1)R agonist, was significantly decreased in both maternal (P<0.05) and fetal brain (P<.01), suggesting a desensitization of the A(1)R/adenylyl cyclase pathway. Therefore, these results suggest that R-PIA intake during pregnancy causes desensitization of the A(1)R-mediated inhibitory transduction pathway in both maternal and fetal brain, probably due to the decreased density of A(1)R at the cell surface.
-
Retinal bipolar cells relay visual information from photoreceptors to third-order retinal neurons. Bipolar cells, comprising multiple types, play an essential role in segregating visual information into multiple parallel pathways in the retina. The identification of molecular markers that can label specific retinal bipolar cells could facilitate the investigation of bipolar cell functions in the retina. ⋯ GFP expression in retinal cone bipolar cells was seen as early as postnatal day 5. In addition, despite severe retinal degeneration due to the presence of the rd1 mutation in this transgenic line, the density of GFP-labeled cone bipolar cells remained stable up to at least 6 months of age. This transgenic mouse line will be a useful tool for the study of type 4 cone bipolar cells in the retina under both normal and disease conditions.