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Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to the elevated T-maze.
Peptides 2004; 25(11):1935-41P

Abstract

The neuropeptide cholecystokinin (CCK) has been implicated in fear and anxiety. CCK is found in the CNS in several molecular forms such as the tetrapeptide (CCK-4) and, mainly, the sulfated octapeptide (CCK-8s) fragments. Administration of CCK-4 induces panic attacks in humans and increases the expression of different anxiety-related behaviors in laboratory animals. The effects of CCK-8s on fear and anxiety are less straightforward and seem to be influenced, among other factors, by the route of the peptide administration and the animal model employed. In other to further investigate the role of CCK-8s in fear and anxiety, in the present study we analyzed the effect of CCK-8s in male Wistar rats submitted to the elevated T-maze. This animal model of anxiety was developed in order to separate generalized anxiety (inhibitory avoidance) and panic-like (escape) responses in the same rat. The effect of CCK-8s in this test was also investigated after injection of the peptide into the dorsal periaqueductal gray (DPAG). This brainstem area is rich in CCK receptors and has consistently been implicated in the mediation of fear and anxiety responses. The results showed that both the intraperitoneal and intra-DPAG injections of CCK-8s potentiated one-way escape behavior, suggesting a panicogenic action. In contrast, the injection of the CCK2 receptor antagonist CR2945 inhibited the expression of this behavior, a panicolytic-like effect. Therefore, the elevated T-maze, in contrast to other animal models of anxiety, can detect the anxiety-eliciting effects of CCK-8s both after its systemic and central administration. Also, the results provide further evidence about the involvement of a CCK-mediated mechanism within the DPAG in the regulation of panic-related defensive behaviors.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15501525

Citation

Zanoveli, Janaina Menezes, et al. "Systemic and Intra-dorsal Periaqueductal Gray Injections of Cholecystokinin Sulfated Octapeptide (CCK-8s) Induce a Panic-like Response in Rats Submitted to the Elevated T-maze." Peptides, vol. 25, no. 11, 2004, pp. 1935-41.
Zanoveli JM, Netto CF, Guimarães FS, et al. Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to the elevated T-maze. Peptides. 2004;25(11):1935-41.
Zanoveli, J. M., Netto, C. F., Guimarães, F. S., & Zangrossi, H. (2004). Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to the elevated T-maze. Peptides, 25(11), pp. 1935-41.
Zanoveli JM, et al. Systemic and Intra-dorsal Periaqueductal Gray Injections of Cholecystokinin Sulfated Octapeptide (CCK-8s) Induce a Panic-like Response in Rats Submitted to the Elevated T-maze. Peptides. 2004;25(11):1935-41. PubMed PMID: 15501525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic and intra-dorsal periaqueductal gray injections of cholecystokinin sulfated octapeptide (CCK-8s) induce a panic-like response in rats submitted to the elevated T-maze. AU - Zanoveli,Janaina Menezes, AU - Netto,Cristina Ferreira, AU - Guimarães,Francisco Silveira, AU - Zangrossi,Hélio,Jr PY - 2004/04/15/received PY - 2004/06/23/revised PY - 2004/06/24/accepted PY - 2004/10/27/pubmed PY - 2005/4/22/medline PY - 2004/10/27/entrez SP - 1935 EP - 41 JF - Peptides JO - Peptides VL - 25 IS - 11 N2 - The neuropeptide cholecystokinin (CCK) has been implicated in fear and anxiety. CCK is found in the CNS in several molecular forms such as the tetrapeptide (CCK-4) and, mainly, the sulfated octapeptide (CCK-8s) fragments. Administration of CCK-4 induces panic attacks in humans and increases the expression of different anxiety-related behaviors in laboratory animals. The effects of CCK-8s on fear and anxiety are less straightforward and seem to be influenced, among other factors, by the route of the peptide administration and the animal model employed. In other to further investigate the role of CCK-8s in fear and anxiety, in the present study we analyzed the effect of CCK-8s in male Wistar rats submitted to the elevated T-maze. This animal model of anxiety was developed in order to separate generalized anxiety (inhibitory avoidance) and panic-like (escape) responses in the same rat. The effect of CCK-8s in this test was also investigated after injection of the peptide into the dorsal periaqueductal gray (DPAG). This brainstem area is rich in CCK receptors and has consistently been implicated in the mediation of fear and anxiety responses. The results showed that both the intraperitoneal and intra-DPAG injections of CCK-8s potentiated one-way escape behavior, suggesting a panicogenic action. In contrast, the injection of the CCK2 receptor antagonist CR2945 inhibited the expression of this behavior, a panicolytic-like effect. Therefore, the elevated T-maze, in contrast to other animal models of anxiety, can detect the anxiety-eliciting effects of CCK-8s both after its systemic and central administration. Also, the results provide further evidence about the involvement of a CCK-mediated mechanism within the DPAG in the regulation of panic-related defensive behaviors. SN - 0196-9781 UR - https://www.unboundmedicine.com/medline/citation/15501525/Systemic_and_intra_dorsal_periaqueductal_gray_injections_of_cholecystokinin_sulfated_octapeptide__CCK_8s__induce_a_panic_like_response_in_rats_submitted_to_the_elevated_T_maze_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(04)00283-9 DB - PRIME DP - Unbound Medicine ER -