Natural activation of caspase-3 is required for the development of operant behavior in postnatal ontogenesis
- 46 Downloads
We have previously demonstrated transient increases in caspase-3 activity in the hippocampus of rat pups from age 17 days. We report here our studies on the effects of inhibition of caspase-3 during this period on the acquisition of a two-way avoidance reaction. Rat pups received intracerebroventricular doses of the caspase-3 inhibitor Z-DEVD-FMK On postnatal day 18. Control animals of the same age received the inactive peptide Z-FA-FMK or isotonic saline solution. Inhibition of caspase-3 during the period of its natural activation in the hippocampus during early ontogenesis was found to impair the development of operant behavior in rats. This was apparent as a reduction in the efficiency of learning during acquisition of active avoidance reactions and decreases in the numbers of intersignal reactions. Administration of the inhibitor had no specific action on the types of conditioned reflex activity less associated with operant learning. Thus, there were no differences between the experimental and control groups in the numbers of emotional reactions to the conditioned stimulus. The number of orientational-investigative conditioned reactions also showed no change after administration of Z-DEVD-FMK. On the background of the reduction in the efficiency of the acquisition of the conditioned active avoidance reflex, the number of incomplete acts, in contrast to other types of conditioned reactions, increased significantly after administration of Z-DEVD-FMK, which is evidence for the persistence of the ability to form associative connections between activation of the conditioned signal and the need to move to the other sector. The difficulty in these animals arose at the decision-taking stage on choosing the appropriate form of behavior. Changes in orientational-investigative behavior were not associated with inhibition of caspase-3 during the critical period of development, as the effects of Z-DEVD-FMK and Z-FA-FMK were similar.
Key Wordsconditioned active avoidance reflex operant behavior postnatal development caspase-3
Unable to display preview. Download preview PDF.
- 1.P. M. Balaban and N. V. Gulyaeva, “The common nature of the molecular mechanisms of neuroplasticity and neuropathology: an integrative approach,” Ros. Fiziol. Zh. 92, No. 2, 145–151 (2006).Google Scholar
- 2.N. V. Gulyaeva, “Te non-apoptotic functions of caspase-3_in the nervous system,” Biokhimiya, 68, No. 11, 1459–1470 (2003).Google Scholar
- 3.I. E. Kudryashov, A. A. Yakovlev, I. V. Kudryashova, and N. V. Gulyaeva, “Inhibition of caspase-3_blocks long-term potentiation in hippocampal slices,” Zh. Vyssh. Nerv. Deyat., 53, No. 5, 537–540 (2003).Google Scholar
- 4.I. V. Kudryashova, “Responses of hippocampal neurons at different stages of acquisition of conditioned reflex avoidance in rats,” Zh. Vyssh. Nerv. Deyat., 51, No. 2, 182–188 (2001).Google Scholar
- 5.I. V. Kudryashova, “Postnatal development of conditioned reflex behavior: comparison of the maturation periods of plastic processes in the hippocampus of rats,” Zh. Vyssh. Nerv. Deyat., 54, No. 5, 666–672 (2004).Google Scholar
- 6.M. Yu. Stepanichev, I. V. Kudryashova, A. A. Yakovlev, O. N. Vorontsova, N. A. Lazareva, and N. V. Gulyaeva, “Studies of the effects of intracerebroventricular administration of the caspase-3 inhibitor Z-DEVD-FMK on behavior in rats,” Zh. Vyssh. Nerv. Deyat., 56, No. 2, 247–256 (2006).Google Scholar
- 11.N. V. Gulyaeva, “'Apoptotic’ mechanisms in normal brain plasticity: caspase-3 and long-term potentiation,” Zh. Vyssh. Nerv. Deyat., 54, No. 4, 437–447 (2004).Google Scholar
- 24.K. Zielinski and E. Nikolaev, “Changes of intertrial response rate with elapse of time after two-way avoidance trial in rats,” Acta Neurobiol. Exp., 57, No. 1, 41–47 (1997).Google Scholar