Amphetamine-evoked rotation requires newly synthesized dopamine at 14 days but not 1 day after intranigral 6-OHDA and is consistently dissociated from sensorimotor behavior

Immediately after unilateral, intranigral 6-hydroxydopamine (6-OHDA), amphetamine (AMPH) evokes “paradoxical” contraversive rotation, whereas 14 days later, AMPH evokes the traditional ipsiversive rotation used to model the chronic Parkinsonian state. In this study, the hypothesis was that accelerated dopamine (DA) synthesis ipsilateral to the lesion augments cytoplasmic DA to produce paradoxical rotation. Therefore, the sensitivity to synthesis inhibition of AMPH-evoked rotation at 1 or 14 days after 6-OHDA was assessed. To determine the functional status that might be reflected by paradoxical rotation, sensorimotor abilities were examined at 1 and 14 days following unilateral 6-OHDA using the elevated swing, paw placement, grip strength, ladder walking, somatosensory neglect, and cylinder tests. At 14 days after 6-OHDA when AMPH-evoked ipsiversive rotation is mediated by the intact hemisphere, rotation was dose-dependently reduced by tyrosine hydroxylase (TH) inhibition with α-methyl-p-tyrosine (α-MPT) or dopa decarboxylase (DDC) inhibition with 3-hydroxybenzyl hydrazine (NSD-1015), indicating dependence upon newly synthesized DA. Conversely, at 1 day after 6-OHDA, paradoxical rotation, presumably mediated by the treated hemisphere, was completely resistant to synthesis blockade, indicating an abundant supply of intracellular DA that is independent from synthesis rates. Sensorimotor behaviors were not correlated with AMPH-evoked rotation. The present data do not support the hypothesis that enhanced DA synthesis is required to express paradoxical rotation. Therefore, alternative mechanisms that may enhance cytoplasmic DA to produce paradoxical rotation are discussed.