Apomorphine-induced changes in local cerebral blood flow in normal rats and after lesions of the dopaminergic nigrostriatal bundle

Systemic administration of the dopamine (DA) receptor agonist apomorphine leads to a general increase in cerebral blood flow (CBF) as determined by the autoradiographic iodoantipyrine technique. The magnitude of the increase varies between different regions but shows no obvious relation to the density of either DA terminals or receptors. The circulatory response is much more prominent in the lateral than in the medial caudate-putamen. Apomorphine seems to increase CBF both via a change in metabolic rate and via stimulation of dilatory vascular receptors. In animals with unilateral 6-hydroxydopamine lesions of the ascending DA pathways apomorphine induces an augmented CBF response in some denervated structures, notably caudate-putamen and globus pallidus. It is concluded that this is partly due to stimulation of denervated supersensitive vascular receptors, suggesting a direct dopaminergic control of the blood vessels in these areas.

[1]  J. Ginos,et al.  Monoamine oxidase and cerebral uptake of dopaminergic drugs. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J. Palacios,et al.  [3H]Spiperone binding sites in brain: autoradiographic localization of multiple receptors , 1981, Brain Research.

[3]  B. K. Hartman,et al.  The use of dopamine -hydroxylase as a marker for the central noradrenergic nervous system in rat brain. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[4]  A. Björklund,et al.  Organization of Catecholamine Neurons in the Rat Central Nervous System , 1978 .

[5]  M. Kuhar,et al.  Dopamine receptors in the rat frontal cortex: An autoradiographic study , 1979, Brain Research.

[6]  T. Hökfelt,et al.  Evidence for dopamine receptor stimulation by apomorphine , 1967, The Journal of pharmacy and pharmacology.

[7]  U. Ungerstedt,et al.  Striatal efferent fibers play a role in maintaining rotational behavior in the rat , 1977, Science.

[8]  J. Mcculloch,et al.  Effects of apomorphine upon local cerebral blood flow. , 1979, European journal of pharmacology.

[9]  O. Lindvall,et al.  Effects of metamphetamine on blood flow in the caudate-putamen after lesions of the nigrostriatal dopaminergic bundle in the rat , 1981, Brain Research.

[10]  J. McNay,et al.  An investigation of the structural requirements for dopamine-like renal vasodilation: phenylethylamines and apomorphine. , 1968, The Journal of pharmacology and experimental therapeutics.

[11]  O. Lindvall,et al.  Cerebral circulatory response to hypercapnia: Effects of lesions of central dopaminergic and serotoninergic neuron systems , 1981, Brain Research.

[12]  J. Mcculloch,et al.  Vasomotor response of cerebral blood vessels to dopamine and dopaminergic agonists. , 1978, Advances in neurology.

[13]  R. Wurtman,et al.  Decrease in neostriatal blood flow after d-amphetamine administration or electrical stimulation of the substantia nigra , 1977, Brain Research.

[14]  S. R. Snodgrass,et al.  Effects of substantia nigra lesions on forebrain 2-deoxyglucose retention in the rat , 1980, Brain Research.

[15]  J. Mcculloch,et al.  Cerebral circulation: effect of stimulation and blockade of dopamine receptors. , 1977, The American journal of physiology.

[16]  John F. Marshall,et al.  Plasticity of [14C]2-deoxy-d-glucose incorporation into neostriatum and related structures in response to dopamine neuron damage and apomorphine replacement , 1980, Brain Research.

[17]  A. Björklund,et al.  The aluminum-formaldehyde (ALFA) histofluorescence method for improved visualization of catecholamines and indoleamines. 1. A detailed account of methodology for central nervous tissue using paraffin, cryostat or vibratome sections , 1980, Journal of Neuroscience Methods.

[18]  S. Iversen,et al.  Regulatory impairments following selective kainic acid lesions of the neostriatum , 1980, Behavioural Brain Research.

[19]  Helen E. Savaki,et al.  The distribution of alterations in energy metabolism in the rat brain produced by apomorphine , 1982, Brain Research.

[20]  S. Iversen,et al.  Neurotoxic lesions of ventrolateral but not anteromedial neostriatum in rats impair differential reinforcement of low rates (DRL) performance , 1982, Behavioural Brain Research.

[21]  U. Ungerstedt,et al.  Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigro-striatal dopamine system. , 1971, Acta physiologica Scandinavica. Supplementum.

[22]  M. Ingvar,et al.  Local versus regional cerebral blood flow in the rat at high (hypoxia) and low (phenobarbital anesthesia) flow rates. , 1979, Acta physiologica Scandinavica.

[23]  U. Ungerstedt,et al.  Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. , 1970, Brain research.

[24]  M. Ingvar,et al.  Effect of Propranolol on Local Cerebral Blood Flow under Normocapnic and Hypercapnic Conditions , 1981, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  S. Snyder,et al.  Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. , 1977, Science.

[26]  J. Mcculloch,et al.  Heterogeneous depression of glucose utilization in the caudate nucleus by GABA agonists , 1981, Brain Research.

[27]  W H Oldendorf,et al.  Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. , 1971, The American journal of physiology.