The substantia nigra pars reticulata mediates the enhancement of startle by the dopamine D1 receptor agonist SKF 82958 in rats.
OBJECTIVE
Several studies have shown that the substantia nigra pars reticulata (SNr) is a critical site of action mediating dopamine agonist effects on motor behaviors. Because dopaminergic and GABA ergic mechanisms may interact in the SNr, we tested the contribution of both dopamine and GABA receptors in the SNr on the enhancement of startle by the dopamine D1 agonist SKF 82958.


METHODS
Male Sprague-Dawley rats were implanted with cannulae into the SNr and 1 week later infused with either the D1 antagonist SCH 23390 (0.1, 1 microg) or the GABA(A) antagonist bicuculline (0.1 microg), followed by a systemic challenge with the D1 agonist SKF 82958 (1 mg/kg). Other rats were infused with the GABA(A) agonist muscimol (0.1 microg) or SKF 82958 (0.1, 1, 5 microg).


RESULTS
Both SCH 23390 and bicuculline infused into the SNr completely blocked the enhancement of startle by systemic SKF 82958. Muscimol infused into the SNr produced a significant increase in startle by itself, whereas SKF 82958 had no effect.


CONCLUSIONS
These results suggest that activation of D1 receptors in the SNr is necessary for the enhancement of startle by SKF 82958, but that activation of these receptors alone is not sufficient to increase startle. These results also suggest that GABA transmission in the SNr may be involved in the enhancement of startle by SKF 82958. Based on these data, we propose that activation of striatonigral neurons by D1 receptor agonists facilitates GABA release in the SNr to produce the observed enhancement of startle.
Meloni
Edward G
EG
Department of Psychiatry and Behavioral Sciences, Emory University, 1639 Pierce Drive, Suite 4000, Atlanta, GA 30322, USA.
Davis
Michael
M
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000037:antagonists & inhibitors; D013216:Reflex, Startle / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects*
D001552:Benzazepines; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D017447:Receptors, Dopamine D1; C071262:SK&F 82958; D001640:Bicuculline