Increased drinking after intra-striatal injection of the dopamine D2/D3 receptor agonist quinpirole in the rat

Dopamine D2 receptor hyperactivity has been implicated in the development of psychogenic polydipsia in schizophrenic patients. Repeated treatment with dopamine agonists, including the D2/D3 agonist quinpirole, has been shown to induce hyperdipsia in a number of animal models. Despite these observations, obtained with systemic administrations, little attempt has been made to investigate where in the brain dopamine agonists act to induce hyperdipsia. The present study investigates the effects of repeated intra-caudate infusions of quinpirole on the intake of water by rats tested under free-drinking conditions. Rats with bilateral cannulae placed into the anterior, central or posterior caudate received quinpirole microinfusions (1 mu g/side) for five consecutive days in their home cage. Water intake was measured 15 and 60 min after the treatment. When injected in the central caudate, quinpirole increased water intake, and this effect progressively increased over sessions, indicating the development of sensitization. When injected in the posterior caudate, the dipsogenic effect of quinpirole was less intense and did not undergo sensitization. The infusion of quinpirole in the anterior caudate did not affect drinking. The present study shows that caudate D2/3 receptors play an important role in the development of quinpirole-induced hyperdipsia, an animal model of psychotic polydipsia.