title: Acetazolamide potentiates the afferent drive to prefrontal cortex in vivo.
abstract: The knowledge on real-time neurophysiological effects of acetazolamide is still far behind the wide clinical use of this drug. Acetazolamide - a carbonic anhydrase inhibitor - has been shown to affect the neuromuscular transmission, implying a pH-mediated influence on the central synaptic transmission. To start filling such a gap, we chose a central substrate: hippocampal-prefrontal cortical projections; and a synaptic phenomenon: paired-pulse facilitation (a form of synaptic plasticity) to probe this drug's effects on interareal brain communication in chronically implanted rats. We observed that systemic acetazolamide potentiates the hippocampal-prefrontal paired-pulse facilitation. In addition to this field electrophysiology data, we found that acetazolamide exerts a net inhibitory effect on prefrontal cortical single-unit firing. We propose that systemic acetazolamide reduces the basal neuronal activity of the prefrontal cortex, whereas increasing the afferent drive it receives from the hippocampus. In addition to being relevant to the clinical and side effects of acetazolamide, these results suggest that exogenous pH regulation can have diverse impacts on afferent signaling across the neocortex.
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Lezio S
authors.initials: LS
authors.lastname: Bueno-Junior
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Rafael N
authors.initials: RN
authors.lastname: Ruggiero
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Matheus T
authors.initials: MT
authors.lastname: Rossignoli
authors.affiliation: Department of Morphology, Physiology and Stomatology, Dentistry School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil.
authors.forename: Elaine A
authors.initials: EA
authors.lastname: Del Bel
authors.affiliation: Department of Neuroscience and Behavioral Sciences, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil jpleite@fmrp.usp.br.
authors.forename: Joao P
authors.initials: JP
authors.lastname: Leite
authors.affiliation: Department of Physiology, Molecular and Cell Biology, Institute of Physiology Molecular Biology and Neuroscience University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Osvaldo D
authors.initials: OD
authors.lastname: Uchitel
mesh_terms: D000086:Acetazolamide / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000502:physiology; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D000086:Acetazolamide
keywords: Carbonic anhydrase; hippocampus; prefrontal cortex; single‐unit activity; synaptic plasticity