Coexistence of D3 R typical and atypical signaling in striatonigral neurons during dopaminergic denervation. Correlation with D3 nf expression changes.

Dopamine D3 R are widely expressed in basal ganglia where interact with D1 R. D3 R potentiate cAMP accumulation and GABA release stimulated by D1 R in striatonigral neurons through "atypical" signaling. During dopaminergic denervation, D3 R signaling changes to a "typical" in which antagonizes the effects of D1 R, the mechanisms of this switching are unknown. D3 nf splice variant regulates membrane anchorage and function of D3 R and decreases in denervation; thus, it is possible that D3 R signaling switching correlates with changes in D3 nf expression and increases of membranal D3 R that mask D3 R atypical effects. We performed experiments in unilaterally 6-hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D3 nf, but not of D3 R in the denervated striatum. Proximity ligation assay showed that D3 R-D3 nf interaction decreased after denervation, whereas binding revealed an increased Bmax in D3 R. The new D3 R antagonized cAMP accumulation and GABA release stimulated by D1 R; however, in the presence of N-Ethylmaleimide (NEM), to block Gi protein signaling, activation of D3 R produced its atypical signaling stimulating D1 R effects. Finally, we investigated if the typical and atypical effects of D3 R modulating GABA release are capable of influencing motor behavior. Injections of D3 R agonist into denervated nigra decreased D1 R agonist-induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D3 R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D3 nf and D3 R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior.

Effects of chronic solvent abuse exposure on umami taste perception.

Inhalant abuse constitutes an important public health problem in Mexico that is more prevalent among children and adolescents. Commercial products that are abused are complex mixtures of solvents containing mainly toluene, in association with other solvents like benzene and xylene. Epidemiological evidence indicates that chronic solvent abuse exposure can cause loss of appetite among other unwanted effects. The mechanisms by which loss of appetite is produced are unknown. It is a matter of interest to determine if loss of appetite is related to changes in taste perception. One of the basic flavors detected by the taste system is umami taste (monosodium glutamate) and it has been proposed that glutamatergic receptors can play an important role in umami taste transduction and perception. It is unknown however, if chronic solvent abuse exposure can induce alterations in umami taste perception. The purpose of this work was to determine if chronic solvent exposure in rats causes alterations in glutamate solution consumption. Rats were exposed to solvents (6000 ppm) in a static chamber for 2 months, as follows: a toluene group, a benzene group, a xylene group and a control group. During the treatment, glutamate solution (120 mM) consumption, food intake and rat weights were measured. The results show that glutamate solution intake was increased in rats chronically exposed to solvents, with differences in consumption patterns between solvents. In addition, chronically exposed animals had a lower weight increase compared with unexposed rats. These data suggest that solvent inhalation originates feeding behavior alteration in rats.