Partial lesions of the nigrostriatal pathway in the rat. Acceleration of transmitter synthesis and release of surviving dopaminergic neurones by drugs.
In rats with partial, unilateral lesions of the dopaminergic nigrostriatal pathway, synthesis of dopamine (DA) per surviving neurone was assessed by measuring the ratio of DOPA accumulated after inhibition of aromatic amino acid decarboxylase to dopamine (DOPA/DA ratio). Release of DA per surviving neurone was assessed by measuring the ratios of the concentrations of 3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) to DA. In striata ipsilateral to the lesion, the DOPA/DA ratio was elevated 4-fold, and the DOPA/DA and HVA/DA ratios were elevated 2-fold as compared to values in contralateral striata. Administration of gamma-butyrolacetone (750 mg/kg, 30 min), i.e. of a drug which accelerates synthesis of DA, further increased the DOPA/DA ratio in lesioned striata to levels 37 times higher than those measured on the control side of saline-injected controls. Morphine (20 mg/kg, 30 min) and haloperidol (2.5 mg/kg, 60 min), i.e. drugs known to accelerate the turnover and release of DA, further elevated the DOPAC/DA and HVA/DA ratios in lesioned striata to levels approx. 5 times higher than the ratios measured on contralateral sides of saline-treated controls. The data indicate that dopaminergic neurones surviving partial lesions of the nigrostriatal pathway synthesize and release DA at an elevated but submaximal rate. Synthesis and release of DA can be further enhanced to a large extent by drugs.
Hefti
F
F
Enz
A
A
Melamed
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000503:physiopathology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000503:physiopathology; D018377:Neurotransmitter Agents / Q000096:biosynthesis*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D006892:Hydroxydopamines; D018377:Neurotransmitter Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D005680:gamma-Aminobutyric Acid; D004295:Dihydroxyphenylalanine; D009020:Morphine; D016627:Oxidopamine; D006220:Haloperidol; D004298:Dopamine; D006719:Homovanillic Acid