Adaptive responsiveness of some central receptors to the denervation of heterologous afferent fibers: functional significance and possible behavioral consequences.

As shown in the rat brain, the development of the classical "denervation supersensitivity" of receptors does not always occur despite the complete destruction of the corresponding afferent fibers. This is due to the concomitant destruction of heterologous fibers which directly or indirectly contribute to the regulation of the denervated receptors. In this review, on the basis of data obtained in rats with lesions of ascending DA neurons, three examples of hetero-regulation of receptors will be provided. In the prefrontal cortex, the concomitant destruction of afferent noradrenergic fibers (NA) prevents the development of the denervation supersensitivity of DA receptors of the D1 type. In the nucleus accumbens, the development of the denervation supersensitivity of D1 receptors seems to be dependent on the state of activity of the cortico-nucleus accumbens glutamatergic projection. Finally, in cortico-limbic structures, the prolonged interruption of DA transmission leads to an increased density of 125I-neurotensin binding sites. These hetero-regulations reflect the existence of possible functional relationships between the two types of neuronal populations under investigation. As an example, it will be shown that some dysfunctions seen following the degeneration of the mesocortico-prefrontal and mesolimbic DA neurons disappear following the combined destruction of ascending NA neurons.