Dopaminergic supersensitivity: influence of dopamine agonists, cholinergics, anticholinergics, and drugs used for the treatment of tardive dyskinesia.

Single and repeated administration of neuroleptics induce supersensitivity to dopamine agonists like apomorphine and methylphenidate. The degree of this supersensitivity depends on the period of the preceding administration of the neuroleptic. In the development phase additional administration of apomorphine can reverse the hyperdopaminergic behaviour, whereas addition of cholinergic/anticholinergic treatment does not modify the enhanced receptor response. In the supersensitivity phase additional treatment with deanol does not modify the supersensitivity. Pheobarbital, diazepam, and muscimol increase and cis (Z)-flupenthixol decreases the supersensitivity. It is concluded that supersensitivity induced by neuroleptics is time-dependent and that it can be prevented by additional treatment with DA-agonists but not by cholinergic/anticholinergic treatment. In the supersensitivity phase, the syndrome is suppressed by dopamine antagonists but enhanced by GABA-agonists, benzodiazepine and phenobarbital.