Amelioration of experimental parkinsonism by intrahypothalamic administration of haloperidol

Accumulation of amines in the degenerating axons of ascending catecholamine-containing neurons in the hypothalamus has been proposed as a site of function neurotransmitter release and may thereby participate in the development of motor impairment seen after central dopamine-depleting lesions. To test this hypothesis further the dopamine receptor antagonist haloperidol (1 microL of a 14 nmol solution) was injected directly into the lateral hypothalamus (LH) in 6 different injection regimes to determine whether amphetamine-induced turning could be attenuated with this treatment. The injection of haloperidol at 1 and 24 h (group 1), 24 h (group 2) or 6+ 7 d (group 3) after 6-hydroxydopamine (6-OHDA) did not modify amphetamine-induced turning. However, the injection of haloperidol at 1 h, 24 h, 7 d, and 8 d (group 4), days 1-7 (group 5), or gradual infusion (14 nmol/microliters/h) for 7 days (group 6) all reduced the 6-OHDA-induced turning to a level similar to that of controls. These results add further support to the contention that amines are released from the axons of degenerating neurones in the hypothalamus and that this phenomenon participates in the elicitation of behavioral impairment attributed solely to the loss of functional neurotransmitters from terminal fields. Furthermore, the data emphasize the importance of hypothalamic pathology in the development of Parkinsonism and suggest that intrahypothalamic administration of dopamine blocking agents might be useful in the treatment of Parkinsonism.