title: Dopamine action in the substantia nigra pars reticulata: iontophoretic studies in awake, unrestrained rats.
abstract: Dopamine (DA) neurons located in the substantia nigra pars compacta release DA not only via axonal terminals, affecting neurotransmission within the striatum, but also via dendrites, some of which densely protrude into the substantia nigra pars reticulata (SNr). Although the interaction of dendritically released DA with somatodendritic autoreceptors regulates DA cell activity, released DA may also affect SNr neurons. These cells, however, lack postsynaptic DA receptors, making it unclear how locally released DA modulates their activity. Although previous work in brain slices suggests that DA might modulate the activity of GABA inputs, thus affecting SNr neurons indirectly, it remains unclear how increased or decreased DA release might affect these cells exposed to normal afferent inputs. To explore this issue, we examined the effects of iontophoretic DA and amphetamine on SNr neurons in awake, unrestrained rats. DA had no consistent effects on SNr cells but amphetamine, known to induce DA release, dose-dependently inhibited most of them. This effect was blocked by SCH23390, a selective D1 receptor blocker, which itself strongly increased neuronal discharge rate. As GABA input is a major factor regulating the activity of SNr neurons, our data suggest that dendritically released DA, by interacting with D1 receptors on striato-nigral and pallido-nigral afferents, is able to decrease this input, thus releasing SNr neurons from tonic, GABA-mediated inhibition. Surprisingly, a full DA receptor blockade (SCH23390 + eticlopride) did not result in the expected increase in SNr discharge rate, suggesting that other mechanisms are responsible for behavioral abnormalities following acute disruption of DA transmission.
authors.affiliation: Cellular Neurobiology Branch, National Institute on Drug Abuse - Intramural Research Program, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, MD 21224, USA.
authors.forename: François
authors.initials: F
authors.lastname: Windels
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Kiyatkin
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D007478:Iontophoresis / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012457:Salicylamides / Q000494:pharmacology; D013378:Substantia Nigra / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014851:Wakefulness
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D012457:Salicylamides; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; C045989:eticlopride; D004298:Dopamine