Stability of substantia nigra pars reticulata neuronal discharge rates during dopamine receptor blockade and its possible mechanisms.
It is hypothesized that substantia nigra pars reticulata neurons become overactive during a deficit of dopamine transmission. In this study, we examined how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse activity of substantia nigra pars reticulata neurons and their response to iontophoretic gamma-amino-n-butyric acid in awake, unrestrained rats. No changes in discharge rate were found during complete dopamine receptor blockade, but these neurons showed a diminished response to gamma-amino-n-butyric acid, suggesting gamma-amino-n-butyric acid receptor hyposensitivity. This may result from tonic increase in gamma-amino-n-butyric acid input from the striatum and globus pallidus, which are activated during dopamine receptor blockade. As substantia nigra pars reticulata neurons are autoactive and resistant to tonic increases in gamma-amino-n-butyric acid input, changes in their responsiveness to phasic gamma-amino-n-butyric acid inputs, not tonic increase discharge rate, may underlie movement disturbance following dopamine deficit.
Windels
François
F
Cellular Neurobiology Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, Baltimore, Maryland 21224, USA.
Kiyatkin
Eugene A
EA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D011954:Receptors, Dopamine / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D012457:Salicylamides; D005680:gamma-Aminobutyric Acid; C045989:eticlopride