In vivo administration of corticotropin-releasing hormone at remote intervals following ischemia enhances CA1 neuronal survival and recovery of spatial memory impairments: a role for opioid receptors.

Abstract

The contribution of corticotropin-releasing hormone (CRH) in the modulation of ischemia-induced cell death in vivo remains unclear. We characterized the impact of pre-ischemic administration of CRH (0, 0.1, 1, 5 microg, i.c.v., 15 min prior to vessel occlusion) on neuronal damage following global ischemia in rats. The injection of 5 microg CRH led to a 37% increase in CA1 neuronal survival compared to vehicle-treated ischemic animals, while pre-treatment with alpha-helical CRH (9-41) abolished this neuronal protection. A second objective aimed to determine whether CRH protection is maintained over weeks when the peptide is administered at remote time intervals following ischemia. Compared to vehicle-treated ischemic animals, administration of CRH 8h following global ischemia led to a 61% increase in CA1 neuronal survival observed 30 days post-ischemia. Neuronal protection translated into significant improvement of ischemia-induced spatial memory deficits in the radial maze. Finally, our findings demonstrated that selective blockade of kappa- and delta-opioid receptors (using nor-binaltorphimine and naltrindole, respectively) prior to CRH administration significantly reduced CA1 neuronal protection. These findings represent the first demonstration of enhanced neuronal survival following in vivo CRH administration in a global model of ischemia in rats. They also support the idea that CRH-induced neuroprotection involves opioid receptors activation.

• Authors: Charlaine Charron, Sabrina Fréchette, Geneviève Proulx, Hélène Plamondon
• Journal: Behavioural brain research (Behav Brain Res) Vol. 188 Issue 1 Pg. 125-35 (Mar 17 2008) ISSN: 0166-4328 [Print] Netherlands
• PMID: 18055027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Receptors, Opioid, delta
• Receptors, Opioid, kappa
• Corticotropin-Releasing Hormone

Topics

• Analysis of Variance
• Animals
• Brain Ischemia (metabolism, pathology)
• Cell Death (physiology)
• Corticotropin-Releasing Hormone (administration & dosage, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Hippocampus (metabolism, pathology)
• Injections, Intraventricular
• Male
• Maze Learning (physiology)
• Nerve Degeneration (metabolism, prevention & control)
• Neurons (metabolism, pathology)
• Neuroprotective Agents (administration & dosage, metabolism)
• Rats
• Rats, Wistar
• Receptors, Opioid, delta (antagonists & inhibitors, metabolism)
• Receptors, Opioid, kappa (antagonists & inhibitors, metabolism)
• Time Factors