Plasticity of [14C]2-deoxy-D-glucose incorporation into neostriatum and related structures in response to dopamine neuron damage and apomorphine replacement.

Unilateral injections of 6-hydroxydopamine into the lateral hypothalamus or ventral tegmental area that damage extensively the mesotelencephalic dopaminergic projection result in significant hemispheric asymmetries in autoradiographic labeling after [14C]2-deoxy-D-glucose (2DG) administration. The incorporation of this glucose analog into the ipsilateral neostriatum, nucleus accumbens septi, olfactory tubercle, and central nucleus of amygdala is decreased relative to the contralateral hemisphere. Concurrently, structures receiving projections from the neostriatum (globus pallidus, entopeduncular nucleus, and substantia nigra, pars reticulata) show enhanced labeling in the 6-hydroxydopamine-injected hemisphere, as do diencephalic structures receiving basal ganglia inputs (ventromedial nucleus and ventrolateral portion of the ventral anterolateral complex of thalamus, lateral portion of lateral habenular nucleus). Most of these 6-hydroxydopamine-induced asymmetries of [14C]2DG labelling are abolished or reversed by the injection of apomorphine i.p. (0.25 mg/kg) or directly into the denervated neostriatum (5 microgram) 7--20 days postoperatively. The metabolic effecgs of apomorphine administration are prevented by pretreatment with the dopamine receptor blocking agent, haloperidol (2mg/kg i.p., 2 h before). Thus, this autoradiographic technique can be used to demonstrate neostriatal output circuits that show altered metabolic activity in response to diminished or excessive forebrain dopamine receptor stimulation. The relevance of these findings to: (1) the behavioral abberations resulting from damage to mesotelencephalic dopaminergic systems; and (2) the 'denervation supersensitivity' to DA receptor stimulants is discussed.