Histamine H3 receptor activation selectively inhibits dopamine D1 receptor-dependent [3H]GABA release from depolarization-stimulated slices of rat substantia nigra pars reticulata
Section snippets
Measurement of [3H]GABA release from slices of substantia nigra pars reticulata
Slices of substantia nigra pars reticulata (SNr) were dissected from Vibratome-cut slices (300 μm) of rat (Wistar strain, males, approximately 250 g body weight; bred in the Centro de Investigacion) brain and incubated for 20 min at 37°C in 4.5 ml of a modified Krebs–Henseleit solution (composition in mM: NaCl 134, KCl 4.75, MgSO4 1, KH2PO4 1.25, NaHCO3 25, CaCl2 2 and d-glucose 10) gassed continously with O2/CO2 (95:5, v/v). Usually eight to 10 slices of SNr were obtained from each animal. The
Potentiation by sulpiride of depolarization-induced release of [3H]GABA
The release of [3H]GABA from slices of SNr induced by increasing the K+ concentration in the superfusate from 6 to 15 mM was consistently increased by the addition of the dopamine D2 receptor antagonist sulpiride (10 μM) (Fig. 1), although the magnitude of the effect of sulpiride differed between experiments and did not reach statistical significance in one of the three experiments. Basal release of [3H]GABA was not significantly altered by 10 μM sulpiride, as determined by comparison of the
Selectivity of H3 agonist action against D1 receptor-potentiated [3H]GABA release
The results presented above demonstrate that histamine H3 receptor activation results in the inhibition of the depolarization-stimulated release of [3H]GABA from microdissected slices of rat SNr. However, the most striking finding is that H3 agonist action is directed selectively against that fraction of [3H]GABA release dependent on the activation of dopamine D1 receptors on the terminals of the striatal projection neurones. The extent to which [3H]GABA release is D1 agonist dependent[14]under
Conclusions
Depolarization-induced release of [3H]GABA from microdissected slices of rat SNr is strongly potentiated by activation of dopamine D1 receptors on the terminals of striatonigral projection neurons. Activation of histamine H3 receptors on these terminals by histamine or by the H3 agonist immepip selectively inhibits the portion of [3H]GABA release dependent on the presence of a D1 receptor agonist. This action of H3 agonists may be complemented by a partial inhibition of depolarization-induced
Acknowledgements
This work was supported by Grant 1381-PN from CONACyT (Mexico). The visit of J.M.Y. to Mexico was made under the auspices of an exchange agreement between the Royal Society of London and the Academia de la Investigacion Cientifica of Mexico.
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