The paradoxical effects of SKF83959, a novel dopamine D1-like receptor agonist, in the rat acoustic startle reflex paradigm.
While the benzazepine SKF83959 elicits classical behavioral responses associated with dopamine D1 receptors, it also acts as a D1 receptor antagonist biochemically. The paradoxical properties of this agent remain an enigma. In the present study, we sought to determine the behavioral effects of SKF83959 in the rat acoustic startle reflex test. Systemic administration of SKF83959 produced a dose-related increase in the startle amplitude with a stimulus of 105 dB, and a significant group difference was observed between animals treated with 1 mg/kg SKF83959 and vehicle controls. SKF83959 also significantly reduced the latency to startle response to stimuli of 95 dB and 105 dB in a dose-dependent manner. However, unlike classical dopamine D1-like receptor agonists, SKF83959 failed to disrupt prepulse inhibition (PPI) of either the startle amplitude or the latency to startle response; rather, the agent dose-dependently increased the PPI latency to startle response of 105 dB stimulus. These results suggest that the behavioral effects of SKF83959 in the rat acoustic startle reflex paradigm are paradoxical, and these paradoxical effects may be associated with its distinct pharmacological properties.
Zhang
Zhang-Jin
ZJ
Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. zzhang1@usuhs.mil
Jiang
Xiao-Long
XL
Zhang
Steven E
SE
Hough
Christopher J
CJ
Li
He
H
Chen
Jian-Guo
JG
Zhen
Xue-Chu
XC
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000161:Acoustic Stimulation; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D013216:Reflex, Startle / Q000187:drug effects*
D018491:Dopamine Agonists; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C080703:SK&F 83959