Neurochemical Studies of the Mesolimbic Dopaminergic Pathway: Glycinergic Mechanisms and Glycinergic-Dopaminergic Interactions in the Rat Ventral Tegmentum

Abstract: The rat ventral tegmentum (containing somata and dendrites of mesolimbic dopaminergic neurones) contained 1.3 μmnol/g wet weight of glycine. Slices of ventral tegmentum accumulated exogenous ³H]glycine by an energy-, temperature- and sodium-dependent mechanism. The uptake was mediated by two different transport systems; one system with relatively low affinity for glycine ( K_m ∼400 μ m ) and the other a higher affinity for glycine ( K_m ∼ 10 μ m ). Small amino acid analogues of glycine inhibited the uptake process, the most potent being taurine and β-alanine (47% and 44% inhibition, respectively, at 1 m m ). Release of exogenous ³H]glycine by elevated potassium and by protoveratrine A was calcium-dependent and tetrodotoxin-sensitive. Glycine (500 μ m -2 m m ) potentiated the protoveratrine A-induced release of exogenous ³H]dopamine from slices of ventral tegmentum; this potentiation was blocked by strychnine (10 μ m ). A convulsant dose of strychnine elevated the concentration of 3,4-dihydroxyphenylacetic acid in the ventral tegmentum. Glycine is likely to be a transmitter in the ventral tegmentum and to have a role regulating the activity of somatodendritic regions of mesolimbic dopaminergic neurones.