Neurochemical Studies of the Mesolimbic Dopaminergic Pathway: [3H]Spiperone Labels Two Binding Sites in Homogenates of the Nucleus Accumbens of Rat Brain

Abstract

The binding of [3H]spiperone to membranes of the nucleus accumbens of the rat brain is of high affinity, rapid, saturable, reversible and stereospecific. Dissociation and saturation experiments indicated the presence of 2 specific binding sites with apparent dissociation constants of 70 pM and > 1 nM. Specific binding with 25 pM [3H]spiperone represented > 90% of total binding and was displaced by dopaminergic agonists, neuroleptic drugs and ergot derivatives. The rank order of potency for the ergot derivatives was bromocriptine > pergolide > lergotrile, and that for D-2 antagonists was domperidone > sulpiride > molindone > metoclopramide. Noradrenergic, histaminergic and serotonergic components of the binding were not detected. [3H]Spiperone binds to high-affinity sites in homogenates of nucleus accumbens, which are likely to be D-2 receptors.