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Chronic and intra-amygdala administrations of the ACTH(4-9) analog ORG 2766 modulate behavioral changes after
I M van Rijzingen1, W H Gispen, R Dam
1Rudolf Magnus Institute for Neurosciences, Utrecht, The Netherlands.
Abstract:
Microinjection of N-methyl-D-aspartic acid (NMDA, 300 ng/3 microliters) into the left lateral ventricle causes a substantial increase in locomotor activity which can be significantly reduced by a chronic pretreatment with the ACTH(4-9) analogue ORG 2766(1 microgram/0.5 ml saline, subcutaneous (s.c.) every day for 7 days, last injection 24 h before the NMDA-injection). A single dose of ORG 2766 (1 ng/1 microliter) injected into the left central amygdaloid nucleus 30 min before the NMDA-injection was equally effective in reducing the increase in locomotion. Furthermore it counteracted the predominance of contralateral turning induced by the NMDA-injection. The data give support for the idea that ORG 2766 excerts its effects on behavior and neural recovery by modulating NMDA receptor activity in the brain.
Insights
The ACTH(4-9) analogue ORG 2766 reduces NMDA-induced hyperactivity and contralateral turning. This suggests ORG 2766 modulates N-methyl-D-aspartic acid receptor activity for behavioral and neural recovery.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Neuroendocrinology
Background:
- N-methyl-D-aspartic acid (NMDA) receptor overactivation is implicated in various neurological conditions.
- The ACTH(4-9) analogue ORG 2766 is known for its potential neuroprotective and behavioral effects.
- Understanding the interaction between NMDA receptors and ACTH analogues is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effects of the ACTH(4-9) analogue ORG 2766 on NMDA-induced behavioral changes.
- To determine if ORG 2766 can mitigate NMDA-induced hyperactivity and turning behavior.
- To explore the potential role of NMDA receptor modulation in ORG 2766's actions.
Main Methods:
- Microinjection of NMDA into the left lateral ventricle of rodents to induce hyperactivity.
- Chronic subcutaneous pretreatment with ORG 2766.
- Acute injection of ORG 2766 into the central amygdaloid nucleus.
- Assessment of locomotor activity and contralateral turning behavior.
Main Results:
- NMDA injection significantly increased locomotor activity.
- Chronic ORG 2766 pretreatment significantly reduced NMDA-induced hyperactivity.
- A single dose of ORG 2766 into the central amygdaloid nucleus was also effective in reducing hyperactivity.
- ORG 2766 counteracted the NMDA-induced predominance of contralateral turning.
Conclusions:
- The ACTH(4-9) analogue ORG 2766 effectively reduces NMDA-induced hyperactivity and turning behavior.
- ORG 2766's effects appear to be mediated through the modulation of NMDA receptor activity.
- These findings support the potential therapeutic application of ORG 2766 in conditions involving NMDA receptor dysregulation.