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

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

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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.

Original languageEnglish (US)
Pages (from-to)60-69
Number of pages10
JournalNeuroscience
Volume285
DOIs
Publication statusPublished - Jan 9 2015

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Keywords

  • Behavior
  • Cardiovascular
  • GABA
  • Liposomes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Vaz, G. C., Bahia, A. P. C. O., de Figueiredo Müller-Ribeiro, F. C., Xavier, C. H., Patel, K. P., Santos, R. A. S., ... Fontes, M. A. P. (2015). Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system. Neuroscience, 285, 60-69. https://doi.org/10.1016/j.neuroscience.2014.10.067