Early malnutrition attenuates the impairing action of naloxone on spreading depression in young rats

Abstract

Objectives

Malnutrition early in life can disrupt neurotransmitter systems in the brain, affecting its electrophysiological function. The opioid receptor antagonist naloxone can affect the electroencephalogram (EEG) and behavior in animals and humans, and patients under drug-abuse treatment use it as a therapy. The goal of this work in the rat is to determine whether malnutrition early in life modulates the action of naloxone on the excitability-related phenomenon known as cortical spreading depression (CSD).

Methods

Malnutrition was induced by feeding the dams during the gestation and lactation with a low-protein diet (8% protein). Their male pups received a single daily subcutaneous injection of naloxone (10 mg/kg/day) from the 7th to the 28th postnatal day, and were subsequently (30–40 days of life) submitted to a 4-hours CSD recording session, with electrodes at two points at a fixed distance apart on the parietal cortical surface.

Results

Compared to well-nourished rats receiving a 23% protein diet, malnourished animals displayed lower body weights and higher CSD velocities of propagation, confirming the facilitating effect of malnutrition on CSD. Naloxone treatment reduced in well-nourished rats the CSD propagation velocity, as compared to saline-injected controls. In contrast, the naloxone effect was less intense in the malnourished condition, and the CSD velocity difference between malnourished-naloxone and malnourished-saline groups did not reach statistical significance.

Discussion

Data strongly support the involvement of opioid-based mechanisms in excitability-related neural processes, which probably influence CSD propagation, and indicate that early malnutrition attenuates the impairing action of naloxone on CSD.

Keywords:

• Malnutrition
• Brain development
• Opioid system
• Cortical spreading depression

Acknowledgments

The authors thank the Brazilian agencies CAPES (Procad/2007), CNPq (INCT de Neurociencia Translacional No. 573604/2008-8), MS/SCTIE/DECIT (No. 17/2006), FACEPE (APQ0975-4.05/08), and IBN-Net/CNPq for financial support. R.C.A. Guedes is a Research Fellow from CNPq (No. 301190/2010-0).