Volume 17, Number 5,
Issue of March 1, 1997
pp. 1838-1847
Copyright ©1997 Society for Neuroscience
Activation of Amygdala CholecystokininB Receptors
Potentiates the Acoustic Startle Response in the Rat
Received Oct. 16, 1996; revised Dec. 12, 1996; accepted Dec. 16, 1996.
Paul W. Frankland1,
Sheena A. Josselyn1,
Jacques Bradwejn2,
Franco
J. Vaccarino1, 2, and
John S. Yeomans1
1 Department of Psychology, University of Toronto,
Toronto, Ontario, Canada M5S 1A1, and 2 Mood and Anxiety
Division, Clarke Institute of Psychiatry, Toronto, Ontario, Canada M5T
1R8
The acoustic startle reflex is a sensitive index of "anxiety"
and "fear." Potentiation of startle by conditioned and
unconditioned fear stimuli appears to be mediated by the amygdala.
CholecystokininB (CCKB) agonists increase
"anxiety" in laboratory animals and induce "panic" in humans.
Here, we investigate the role CCKB receptor-mediated mechanisms in the amygdala in the potentiation of startle. First, intra-amygdala infusions of the CCKB receptor agonist
pentagastrin (0, 0.01, 0.1, 1, and 10 nM) produced a
dose-related potentiation of acoustic startle responses. At the highest
dose, startle amplitudes were increased up to 90% above preinfusion
baseline levels. Second, similar infusions of pentagastrin had no
effect on locomotor activity over the same time course, showing that
increases in startle responsivity after infusions of pentagastrin are
not attributable to nonspecific changes in motor activity. Third,
infusions of similar doses of pentagastrin into the striatum or nucleus
accumbens did not potentiate startle responses. Fourth, pretreatment
with the CCKB receptor antagonist L-365,260 (0.1 mg/kg,
i.p.) attenuated the potentiation of startle produced by intra-amygdala
infusions of pentagastrin. Finally, intra-amygdala infusion of the
CCKB receptor-selective antagonist PD-135158 (10 µg)
blocked the potentiation of startle produced by i.c.v. infusions of
pentagastrin, suggesting that i.c.v. infusions of pentagastrin
potentiate startle responses via activation of amygdala
CCKB receptors. These results show that amygdala
CCKB receptor-mediated mechanisms are involved in the
potentiation of acoustic startle responses.
Key words:
startle;
anxiety;
fear;
locomotor activity;
i.c.v.;
microinjection;
pentagastrin;
cholecystokinin;
striatum;
PD-135158;
L-365,260