Microinfusion of pituitary adenylate cyclase-activating polypeptide into the central nucleus of amygdala of the rat produces a shift from an active to passive mode of coping in the shock-probe fear/defensive burying test - PubMed (original) (raw)

Comparative Study

Microinfusion of pituitary adenylate cyclase-activating polypeptide into the central nucleus of amygdala of the rat produces a shift from an active to passive mode of coping in the shock-probe fear/defensive burying test

Gabor Legradi et al. Neural Plast. 2007.

Abstract

High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) nerve fibers are present in the central nucleus of amygdala (CeA), a brain region implicated in the control of fear-related behavior. This study evaluated PACAPergic modulation of fear responses at the CeA in male Sprague-Dawley rats. PACAP (50-100 pmol) microinfusion via intra-CeA cannulae produced increases in immobility and time the rats spent withdrawn into a corner opposite to the electrified probe compared to controls in the shock-probe fear/defensive burying test. Shock-probe burying and exploration, numbers of shocks received, locomotion distance, and velocity were all reduced by intra-CeA PACAP injection. Further, intra-CeA PACAP effects were manifested only when the animals were challenged by shock, as intra-CeA PACAP injections did not cause significant changes in the behaviors of unshocked rats. Thus, intra-CeA administration of PACAP produces a distinct reorganization of stress-coping behaviors from active (burying) to passive modes, such as withdrawal and immobility. These findings are potentially significant toward enhancing our understanding of the involvement of PACAP and the CeA in the neural basis of fear and anxiety.

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Figures

Figure 1

Figure 1

Histological verification of an injection site produced by microinjected synthetic PACAP. (a) Section from control brain, injected with aCSF vehicle. (b) Injected synthetic PACAP (50 pmol) immunoreactivity in the CeA. BLA = basolateral nucleus of the amygdala, CeM = central nucleus of the amygdala medial part, CeL = central nucleus of the amygdala, lateral part. Note the presence of high density of endogenous PACAP fibers in both (a) and (b). Arrows indicate the location of cannula track. In (b), synthetic PACAP injection is visible as an intense dark reaction product. Scale bar = 200 _μ_m.

Figure 2

Figure 2

Effects of intra-CeA microinfusion of PACAP on shock-probe exploration and zonal preference in shocked rats. The numbers of probe exploration events (a) and time spent on probe exploration (b) are significantly reduced by intra-CeA PACAP. Zonal preference is altered by intra-CeA PACAP microinjection as rats spent significantly less time in the near zone (c) but more time in the zone away from the electrified shock probe (d). *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 7/group, PACAP50 n = 7/group, PACAP100 n = 4/group).

Figure 2

Figure 2

Effects of intra-CeA microinfusion of PACAP on shock-probe exploration and zonal preference in shocked rats. The numbers of probe exploration events (a) and time spent on probe exploration (b) are significantly reduced by intra-CeA PACAP. Zonal preference is altered by intra-CeA PACAP microinjection as rats spent significantly less time in the near zone (c) but more time in the zone away from the electrified shock probe (d). *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 7/group, PACAP50 n = 7/group, PACAP100 n = 4/group).

Figure 2

Figure 2

Effects of intra-CeA microinfusion of PACAP on shock-probe exploration and zonal preference in shocked rats. The numbers of probe exploration events (a) and time spent on probe exploration (b) are significantly reduced by intra-CeA PACAP. Zonal preference is altered by intra-CeA PACAP microinjection as rats spent significantly less time in the near zone (c) but more time in the zone away from the electrified shock probe (d). *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 7/group, PACAP50 n = 7/group, PACAP100 n = 4/group).

Figure 2

Figure 2

Effects of intra-CeA microinfusion of PACAP on shock-probe exploration and zonal preference in shocked rats. The numbers of probe exploration events (a) and time spent on probe exploration (b) are significantly reduced by intra-CeA PACAP. Zonal preference is altered by intra-CeA PACAP microinjection as rats spent significantly less time in the near zone (c) but more time in the zone away from the electrified shock probe (d). *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 7/group, PACAP50 n = 7/group, PACAP100 n = 4/group).

Figure 3

Figure 3

Effects of intra-CeA PACAP microinjection on locomotion parameters in shocked rats. Total distance moved (a) and mean movement velocity (b) were significantly reduced by intra-CeA PACAP microinjection. Immobility events (c) and total time spent on immobility (d) following probe-contact-induced shocks were increased by intra-CeA PACAP. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 3

Figure 3

Effects of intra-CeA PACAP microinjection on locomotion parameters in shocked rats. Total distance moved (a) and mean movement velocity (b) were significantly reduced by intra-CeA PACAP microinjection. Immobility events (c) and total time spent on immobility (d) following probe-contact-induced shocks were increased by intra-CeA PACAP. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 3

Figure 3

Effects of intra-CeA PACAP microinjection on locomotion parameters in shocked rats. Total distance moved (a) and mean movement velocity (b) were significantly reduced by intra-CeA PACAP microinjection. Immobility events (c) and total time spent on immobility (d) following probe-contact-induced shocks were increased by intra-CeA PACAP. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 3

Figure 3

Effects of intra-CeA PACAP microinjection on locomotion parameters in shocked rats. Total distance moved (a) and mean movement velocity (b) were significantly reduced by intra-CeA PACAP microinjection. Immobility events (c) and total time spent on immobility (d) following probe-contact-induced shocks were increased by intra-CeA PACAP. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 4

Figure 4

Effect of intra-CeA PACAP administration on shock-probe burying and shock-related behaviors. Latency to bury the electrified shock probe (a) was significantly increased in PACAP-injected animals whereas burying events (b) and time (c) and the height of bedding over the probe (d) were reduced. The number of probe-contact-induced shocks (e) was significantly reduced in PACAP-injected animals but shock reactivity (e) was unaltered. *P < .05 and **P ≤ .001 compared to aCSF controls.

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 5

Figure 5

Summary of relevant behaviors of rats tested with the unelectrified shock probe (unshocked groups). Intra-CeA PACAP microinjection, in the absence of shocks, had no significant main effect on rat behaviors in the test chamber. (a) probe exploration events, (b) probe exploration time, (c) near zone time, (d) away zone time, (e) total distance moved, and (f) movement velocity. *P < .05 and **P ≤ .001 compared to aCSF controls. (aCSF n = 6/group, PACAP50 n = 4/group, PACAP100 n = 5/group.)

Figure 6

Figure 6

Grooming and rearing behaviors of shocked and unshocked rats in the shock-probe fear chamber. Intra-CeA PACAP microinjection had no statistically significant effects on grooming events (a) and time (b) or rearing events (c) and time (d) in shocked or unshocked groups of rats, relative to their respective aCSF-injected controls.

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References

    1. Arimura A, Shioda S. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Frontiers in Neuroendocrinology. 1995;16(1):53–88. - PubMed
    1. Morley JE, Horowitz M, Morley PMK, Flood JF. Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice. Peptides. 1992;13(6):1133–1135. - PubMed
    1. Chance WT, Thompson H, Thomas I, Fischer JE. Anorectic and neurochemical effects of pituitary adenylate cyclase activating polypeptide in rats. Peptides. 1995;16(8):1511–1516. - PubMed
    1. Murase T, Kondo K, Otake K, Oiso Y. Pituitary adenylate cyclase-activating polypeptide stimulates arginine vasopressin release in conscious rats. Neuroendocrinology. 1993;57(6):1092–1096. - PubMed
    1. Nomura M, Ueta Y, Serino R, Yamamoto Y, Shibuya I, Yamashita H. Effects of centrally administered pituitary adenylate cyclase-activating polypeptide on c-fos gene expression and heteronuclear RNA for vasopressin in rat paraventricular and supraoptic nuclei. Neuroendocrinology. 1999;69(3):167–180. - PubMed

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