The low affinity component of [3H]spiperone binding reflects association to a non-dopaminergic, neuroleptic site

The pharmacological properties of a low affinity site labelled by [3H]spiperone in membranes prepared from the rat nucleus accumbens were examined by investigating the ability of dopaminergic agonists, antagonists and various other drugs to displace the binding of 2 nM [3H]spiperone. Neuroleptic drugs were the most potent displacers of binding, and dopaminergic agonists, except for bromocryptine and lergotrile, had inhibition constants greater than 1 microM. The majority of drugs studied exhibited a high selectivity for the high affinity site labelled by [3H]spiperone and low affinity sites probably represent a non-specific, non-dopaminergic site for neuroleptic drugs.