Regulatory aspects of nigrostriatal dopaminergic neurons.
In the urethane-anesthetized rat, electrical stimulation (10 Hz, 30 s, 250 microA) of the medial forebrain bundle (MFB), at 20-min intervals over an 8-h period, combined with intracerebral microdialysis in the striatum caused: an undiminished increase in the release of dopamine (DA) with each stimulation episode; a decreased efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA) after the first stimulation only; a delayed increased efflux of DOPAC with no change in HVA; and a poststimulation depression of firing of dopaminergic neurons in the substantia nigra (before, 3.1 +/- 0.7 Hz; after, 1.9 +/- 1.0 Hz; P < 0.05). After the last stimulation episode, the release of DA declined to prestimulation values, while the increased efflux of DOPAC persisted for three more hours. After the infusion of tetrodotoxin (4.0 x 10(-7) M, 1.5 microliters, 1.0 microliters/min) into the MFB, the basal release of DA was reduced (P < 0.05), while the efflux of DOPAC and HVA was increased (P < 0.05). A model is proposed suggesting that: (1) during increased release of DA in the striatum, the metabolism of DA is decreased; (2) inhibition of nigrostriatal dopaminergic neurons is the usual cause of increased synthesis and metabolism of DA in the striatum; and (3) increased release of DA, and increased synthesis and metabolism of DA in the striatum are not causally linked and are noncoupled processes.
Miu
P
P
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Karoum
F
F
Toffano
G
G
Commissiong
J W
JW
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D013779:Tetrodotoxin; D004298:Dopamine; D006719:Homovanillic Acid