Rapidly induced dopaminergic supersensitivity: D1/D2 receptor participation and its prevention by an MAO-inhibitor

The dopaminergic system requires combined dopamine D1/D2 receptor stimulation to express its activity; a phenomenon called synergism D1/D2. Dopamine receptors develop supersensitivity following dopamine de-afferentation and/or reserpine treatment. Acute supersensitivity occurs with reserpine treatment. The breakdown of D1/D2 synergism has been proposed implicating the genesis of this kind of supersensitivity. We sought to determine the best conditions for inducing acute dopaminergic supersensitivity evaluated by apomorphine-induced stereotyped behaviour, to examine whether D1/D2 synergism breakdown occurs in this reserpine-induced acute supersensitivity model, and whether it can be prevented by the monoamino-oxidase (MAO) inhibitor selegiline. Reserpine (2.0 mg/kg) was injected 3 h before apomorphine (0.6 mg/kg) induced stereotypy. D1/D2 synergism was investigated using specific antagonists (D1-SKF 83566 2.5 mg/kg, D2-haloperidol 2.0 mg/kg) and selegiline (10 mg/kg) was used to analyze the influence of dopamine “de-novo” synthesis. All antagonist treatments suppressed stereotypy and selegiline prevented supersensitivity. These data suggest that reserpine-induced acute dopaminergic supersensitivity is not due to the breakdown of D1/D2 synergism and such supersensitivity can be prevented by recently synthesised dopamine.