title: Delayed stress-induced increase in tissue level of cholecystokinin in rat prefrontal cortex: modulation by microdialysis probe implantation and systemic ketamine.
abstract: In the brain, the neuropeptide cholecystokinin (CCK) appears to be involved in the mediation of stress responses. Here we provide new evidence that mild stress induces long-term changes in CCK-like immunoreactivity (CCK-LI) in the prefrontal cortex (PFC). The changes in CCK-LI show a biphasic pattern, with a decrease 20 min after and an increase 8 h after mild stress. These changes seem to be region specific. Measurement of CCK mRNA in prefrontal cortex neurons 4 or 8 h after the stress stimulus did not reveal changes in mRNA levels, suggesting that afferent CCK-containing neuron terminals may be more affected than local cortical CCK-ergic neurons. Furthermore, treatment with the glutamate NMDA receptor antagonist ketamine, led to more pronounced decreases in CCK-LI observed within 20 min after mild stress and counteracted the stress induced increase in cortical CCK-LI levels observed at 8 h. Implantation of a microdialysis probe in the PFC affected the response to mild stress, with no significant decrease in the CCK-LI level 20 min after, and attenuated reactivity to stress 8 h after the saline injection. Our results indicate that a mild stressful stimulus such as an intraperitoneal saline injection may have long-lasting effects on CCK-ergic transmission in the PFC. The use of microdialysis to study stress induced in vivo CCK-LI release in awake animals may, however, be significantly compromised by the impact of the microdialysis probe implantation on CCK-ergic mechanisms in the PFC. In addition, we hypothesize that subanesthetic doses of the psychotomimetic drug ketamine interfere with CCK-ergic mechanisms in the PFC during stress.
authors.affiliation: Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institute, SE-171 76 Stockholm, Sweden. diana.radu@ks.se
authors.forename: D
authors.initials: D
authors.lastname: Radu
authors.forename: E
authors.initials: E
authors.lastname: Brodin
authors.forename: G
authors.initials: G
authors.lastname: Weber
authors.forename: N
authors.initials: N
authors.lastname: Lindefors
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine; D002766:Cholecystokinin