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.