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Updated: Aug 9, 2026
Operant Procedures for Assessing Behavioral Flexibility in Rats
Published on: February 15, 2015
Central administration of a caspase inhibitor impairs shuttle-box performance in rats
M Yu Stepanichev1, I V Kudryashova, A A Yakovlev
1Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerov Street 5A, Moscow 117485, Russia.
Abstract:
Recent studies suggest that caspase-3-mediated mechanisms are essential for neuronal plasticity. N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val- Asp(OMe)-fluoromethyl ketone (z-DEVD-fmk), a caspase inhibitor with predominant specificity toward caspase-3, has been shown to block long-term potentiation in hippocampal slices. Intrahippocampal infusion of a caspase-3 inhibitor to rats has been shown to significantly impair spatial memory in the water maze. The present work was designed to study whether i.c.v. administration of a caspase-3 inhibitor z-DEVD-fmk impairs learning in other tasks related to specific forms of memory in rats. The rats received bilateral injections of z-DEVD-fmk or N-benzyloxycarbonyl-Phe-Ala-fluoromethyl ketone (z-FA-fmk) ("control" peptide) at a dose of 3 nmol. Administration of z-DEVD-fmk significantly decreased the number of avoidance reactions in some blocks of trials in the active avoidance (shuttle box) learning, while z-FA-fmk had no effect as compared with intact rats. However, only a slight effect of the caspase inhibitor across the session was found. z-DEVD-fmk impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings. Measurement of caspase-3 activity in rat brain regions involved in active avoidance learning revealed most expressed z-DEVD-fmk-related inhibition of the enzyme activity (about 30%) in the fronto-parietal cortex. A similar effect was close to significant in the hippocampus, but not in the other cerebral structures studied. In primary cultures of cerebellar neurons z-DEVD-fmk (2-50 microM) inhibited caspase-3 activity by 60-87%. We suggest that moderate inhibition of caspase-3 resulting from the central administration of z-DEVD-fmk to rats may impair active avoidance learning. Taking into account previous data on the involvement of neuronal caspase-3 in neuroplasticity phenomena we assume that the enzyme may be important for selected forms of learning.
Insights
Caspase-3 inhibition impairs active avoidance learning in rats. This suggests the enzyme is crucial for specific memory forms and neuronal plasticity.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Caspase-3 is implicated in neuronal plasticity.
- Caspase-3 inhibition blocks long-term potentiation and impairs spatial memory.
Purpose of the Study:
- To investigate if caspase-3 inhibition affects other learning tasks.
- To determine the impact of caspase-3 inhibitor z-DEVD-fmk on active avoidance learning in rats.
Main Methods:
- Rats received central injections of z-DEVD-fmk (caspase-3 inhibitor) or z-FA-fmk (control).
- Active avoidance learning was assessed using a shuttle box.
- Caspase-3 activity was measured in brain regions.
Main Results:
- z-DEVD-fmk significantly reduced avoidance reactions and impaired components of two-way active avoidance learning.
- z-FA-fmk had no significant effect.
- Caspase-3 activity was inhibited in the fronto-parietal cortex and hippocampus.
Conclusions:
- Moderate central caspase-3 inhibition impairs active avoidance learning.
- Caspase-3 is important for specific forms of learning and neuronal plasticity.
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