title: 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.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: G C
authors.initials: GC
authors.lastname: Vaz
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: A P C O
authors.initials: AP
authors.lastname: Bahia
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: F C
authors.initials: FC
authors.lastname: de Figueiredo Müller-Ribeiro
authors.affiliation: Department of Physiological Sciences, Federal University of Goiás, Goiania, Brazil.
authors.forename: C H
authors.initials: CH
authors.lastname: Xavier
authors.affiliation: Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: K P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: R A S
authors.initials: RA
authors.lastname: Santos
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: F A
authors.initials: FA
authors.lastname: Moreira
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: F
authors.initials: F
authors.lastname: Frézard
authors.affiliation: National Institute of Science and Technology in Nanobiopharmaceutics (INCT - Nanobiofar), Department of Physiology & Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil. Electronic address: peliky@icb.ufmg.br.
authors.forename: M A P
authors.initials: MA
authors.lastname: Fontes
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D062186:Arterial Pressure / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002408:Catheters, Indwelling; D002491:Central Nervous System Agents / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D018682:GABA Agents / Q000008:administration & dosage*; D006339:Heart Rate / Q000187:drug effects; D057967:Infusions, Intraventricular; D007668:Kidney / Q000294:innervation; D008081:Liposomes / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013610:Tachycardia / Q000188:drug therapy / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
chemical_list: D002317:Cardiovascular Agents; D002491:Central Nervous System Agents; D018682:GABA Agents; D008081:Liposomes; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline
keywords: GABA; behavior; cardiovascular; liposomes