Abstract
S(-)3-amino-1-hydroxypyrrolidone-2 (S(-)HA-966), a potent γ-hydroxybutyrate-like drug, inhibits spontaneous firing and induces a pacemaker-like discharge pattern in nigral dopamine (DA)-containing neurons. Recent evidence has suggested that these effects could be mediated by GABAB receptors and, thus, is likely to involve G protein intermediaries. To test this hypothesis, extracellular single-unit recording techniques were used to assess the effects of S(-)HA-966 in animals that had received an intranigral injection of pertussis toxin (PT). Failure to respond to the inhibitory effects of apomorphine was taken as presumptive evidence that PT-sensitive G protein-coupled receptors had been inactivated. No significant differences were observed in the basal firing properties of DA cells recorded in control and PT-lesioned animals. However, in marked contrast to the inhibitory effects observed in uninjected and sham-lesioned animals, S(-)HA-966 significantly increased the firing rate of apomorphine-insensitive DA neurons in PT-lesioned rats. The excitatory effects of S(-)HA-966 were accompanied by a significant reduction in bursting activity and an increase in the regularity of firing. These data indicate that the inhibitory effects of S(-)HA-966 are mediated locally within the substantia nigra by a PT-sensitive substrate, presumably a G protein-coupled receptor.
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Shepard, P., Connelly, S. Pertussis Toxin Lesions of the Rat Substantia Nigra Block the Inhibitory Effects of the γ-Hydroxybutyrate Agent, S(-)HA-966 without Affecting the Basal Firing Properties of Dopamine Neurons. Neuropsychopharmacol 21, 650–661 (1999). https://doi.org/10.1016/S0893-133X(99)00063-9
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DOI: https://doi.org/10.1016/S0893-133X(99)00063-9
