Activation of amygdala cholecystokininB receptors potentiates the acoustic startle response in the rat.
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 micro;g) 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.
Frankland
P W
PW
Department of Psychology, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
Josselyn
S A
SA
Bradwejn
J
J
Vaccarino
F J
FJ
Yeomans
J S
JS
D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D005239:Fear / Q000502:physiology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D007211:Indoles; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C065600:PD 135158; C058121:L 365260; D008536:Meglumine; D010418:Pentagastrin