Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures

Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinase abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated in and required for both the induction of long-term potentiation (LTP) in hippocampal slices and the acquisition of fear conditi...

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Bibliographic Details
Published in:Behavioural brain research 1999-11, Vol.105 (2), p.219-223
Main Authors: Walz, Roger, Roesler, Rafael, Quevedo, João, Rockenbach, Isabel C, Amaral, Olavo B, Vianna, Mônica R.M, Lenz, Guido, Medina, Jorge H, Izquierdo, Iván
Format: Article
Language:English
Subjects:
Animals
Avoidance Learning - drug effects
Behavioral psychophysiology
Biological and medical sciences
Cerebral Cortex - physiology
Depression, Chemical
Dose-Response Relationship, Drug
Entorhinal cortex
Entorhinal Cortex - physiology
Enzyme Inhibitors - administration & dosage
Enzyme Inhibitors - pharmacology
Fear - psychology
Flavonoids - administration & dosage
Flavonoids - pharmacology
Fundamental and applied biological sciences. Psychology
Inhibitory avoidance
Injections
Kinases
Male
MAPK
Memory
Memory - drug effects
Miscellaneous
Mitogen-activated protein kinase
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
Parietal cortex
Parietal Lobe - physiology
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Rats
Rats, Wistar
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Summary:Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinase abundantly expressed in postmitotic neurons of the developed nervous system. MAPK is activated in and required for both the induction of long-term potentiation (LTP) in hippocampal slices and the acquisition of fear conditioning training in rats. The present work was performed in order to test the effect of the specific inhibitor of MAPK kinase (MAPKK), PD 098059, on retention of a step-down inhibitory avoidance (IA). Adult male Wistar rats were bilaterally injected (0.5 μl/side) with PD 098059 (at 0.5, 5, or 50 μM) or vehicle into the entorhinal cortex or into the parietal cortex immediately after IA training using a 0.4 mA footshock. Retention testing was carried out 24 h after training. PD 098059 impaired retention when injected into the entorhinal cortex at the dose of 50 μM, but not at the doses of 5 or 0.5 μM. When infused into the parietal cortex, PD 098059 was amnestic at the doses of 5 and 50 μM. The drug had no effect when infused at the highest dose in either structure 6 h after training. Our results suggest that the MAPKK inhibitor impairs IA retention memory in a dose-dependent manner when injected immediately after training into entorhinal cortex or parietal cortex. The effective dose is variable according to the neocortical structure studied.
ISSN:0166-4328
1872-7549
DOI:10.1016/S0166-4328(99)00077-7