Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

Abstract

Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P < 0.05), blunted tachycardia in the stress trial (ΔHR: GS 115 ± 14, EL 117 ± 10, GL 74 ± 9 bpm; P<0.05) and spent more time in the open arms of elevated plus maze (EL 6 ± 2 vs. GL 18 ± 5%; P = 0.028) compared with GS and EL groups. These results indicate that liposome-entrapped GABA can be a potential tool for exploring the chronic effects of GABA in specific regions and pathways of the central nervous system.

• Authors: G C Vaz, A P C O Bahia, F C de Figueiredo Müller-Ribeiro, C H Xavier, K P Patel, R A S Santos, F A Moreira, F Frézard, M A P Fontes
• Journal: Neuroscience (Neuroscience) Vol. 285 Pg. 60-9 (Jan 29 2015) ISSN: 1873-7544 [Electronic] United States
• PMID: 25446344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Cardiovascular Agents
• Central Nervous System Agents
• GABA Agents
• Liposomes
• bicuculline methiodide
• gamma-Aminobutyric Acid
• Bicuculline

Topics

• Animals
• Anxiety (drug therapy, physiopathology)
• Arterial Pressure (drug effects)
• Bicuculline (administration & dosage, analogs & derivatives)
• Cardiovascular Agents (administration & dosage)
• Catheters, Indwelling
• Central Nervous System Agents (administration & dosage)
• Exploratory Behavior (drug effects, physiology)
• GABA Agents (administration & dosage)
• Heart Rate (drug effects)
• Infusions, Intraventricular
• Kidney (innervation)
• Liposomes (administration & dosage)
• Male
• Microinjections
• Rats, Wistar
• Stress, Physiological (drug effects, physiology)
• Sympathetic Nervous System (drug effects, physiology)
• Tachycardia (drug therapy, physiopathology)
• gamma-Aminobutyric Acid (administration & dosage)