Dopamine Neurone Degeneration-Like Deficits Produced by Intrahypothalamic Dopamine Injections

Summary

When nigro-striatal and mesolimbic dopamine neurones degenerate, a loss of dopamine in various forebrain terminal fields occurs which is accompanied by increased amines in the degenerating axons that traverse the hypothalamus. While the behavioural deficits that occur after nigro-striatal degeneration have been attributed to the loss of dopamine neurotransmission in the striatum, recent evidence supports the contention that the amine accumulation in the degenerating axons represents functional neurotransmitter which may be released from these axons and may thereby participate in the production of behavioural deficits. To test this hypothesis further, albino rats were injected bilaterally with 200 nmol of dopamine in a location just rostral to the diencephalon/mesencephalon border, where amine acctimulation is commonly observed following lateral hypothalmic lesions that reduce forebrain dopamine content. The effect of these injections upon motor performance and thermoregulation was determined 40 minutes after dopamine injection. In a second study, pargyline (50 mg/kg i.p.) was administered 30 minutes before intracerebral dopamine to determine whether this treatment would increase the severity of motor and thermoregulatory deficits which occurred after dopamine injections alone. Deficits in locomotion, rearing, and the ability to regulate body temperature were seen after the dopamine injections. The behavioural deficits displayed by pargyline- pretreated, dopamine-injected animals were slightly but not significantly more severe than those displayed by animals receiving dopamine injections alone, iliese results add further support to the hypothesis that amines which accumulate in degenerating neurones may be neuroactive and may thereby participate in the production of behavioural deficits attributed previously to the loss of dopamine neurotransmission.