Modulation of fear-potentiated startle and vocalizations in juvenile rhesus monkeys by morphine, diazepam, and buspirone.
BACKGROUND
Modulation of the acoustic startle response by aversive sensory stimulation is a simple and objective indicator of emotionality in rodents and human beings that has been extremely valuable for the analysis of neural systems associated with fear and anxiety. We have described a paradigm for measuring fear-potentiated, whole-body acoustic startle in nonhuman primates and have developed a protocol for maintaining fear-potentiated startle over repeated sessions with minimal extinction to allow measurement of pharmacological effects on fear-potentiated startle by using within-subjects designs in relatively small groups of monkeys.


METHODS
A novel, within-subjects testing protocol was used to examine the effects of three compounds in rhesus monkeys that have anxiolytic effects in rodents on fear-potentiated startle but that differ in their mechanism of action. Spontaneous vocalizations during testing also were recorded. Juvenile monkeys that were trained to associate a visual stimulus with a fear-inducing air blast to the face were tested after acute administration of different doses of buspirone diazepam, morphine, or vehicle.


RESULTS
Monkeys rapidly developed a robust and persistent elevation of startle response in the presence of the CS during repeated testing sessions. Diazepam and morphine produced dose-related reductions of fear-potentiated startle. Buspirone did not significantly reduce fear-potentiated startle at the doses tested, although a trend was evident at the highest dose. All drugs reduced rates of coo vocalizations during startle testing.


CONCLUSIONS
These fear-potentiated startle results suggest that rhesus monkeys have a pharmacological profile with respect to these compounds that is closer to humans than to rats. This demonstrates the value of examining the effects of drugs on fear-potentiated startle in nonhuman primates.
Winslow
James T
JT
Yerkes National Primate Research Center, Psychiatry and Behavioral Science, Center for Behavioral Neuroscience, Emory University, Atlanta, Georgia, USA. jameswinslow@mail.nih.gov
Noble
Pamela L
PL
Davis
Michael
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects* / Q000523:psychology*; D007206:Individuality; D008253:Macaca mulatta; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D013216:Reflex, Startle / Q000187:drug effects*; D014828:Vocalization, Animal / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D009294:Narcotics; D009020:Morphine; D003975:Diazepam; D002065:Buspirone