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Hyperactivity and memory/learning deficits evoked by developmental exposure to nicotine and/or ethanol are mitigated by cAMP and cGMP signaling cascades activation.
Abreu-Villaça, Yael; Carvalho-Graça, Anna C; Skinner, Gabriela; Lotufo, Bruna M; Duarte-Pinheiro, Vitor H S; Ribeiro-Carvalho, Anderson; Manhães, Alex C; Filgueiras, Claudio C.
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  • Abreu-Villaça Y; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil. Electronic address: yael_a_v@pq.cnpq.br.
  • Carvalho-Graça AC; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
  • Skinner G; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
  • Lotufo BM; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
  • Duarte-Pinheiro VHS; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
  • Ribeiro-Carvalho A; Departamento de Ciências, Faculdade de Formação de Professores da Universidade do Estado do Rio de Janeiro, São Gonçalo, RJ, 24435-005, Brazil.
  • Manhães AC; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
  • Filgueiras CC; Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro (UERJ), Av. Prof. Manuel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
Neurotoxicology ; 66: 150-159, 2018 05.
Article en En | MEDLINE | ID: mdl-29653137
Pregnant smoking women are frequently episodic drinkers. Here, we investigated whether ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to nicotine aggravates memory/learning deficits and hyperactivity, and associated cAMP and cGMP signaling disruption. To further investigate the role of these signaling cascades, we verified whether vinpocetine (a phosphodiesterase inhibitor) ameliorates the neurochemical and behavioral outcomes. Swiss mice had free access to nicotine (NIC, 50 µg/ml) or water to drink during gestation and until the 8th postnatal day (PN8). Ethanol (ETOH, 5 g/kg, i.p.) or saline were injected in the pups every other day from PN2 to PN8. At PN30, animals either received vinpocetine (20 mg/kg, i.p.) or vehicle before being tested in the step-down passive avoidance or open field. Memory/learning was impaired in NIC, ETOH and NIC + ETOH mice, and vinpocetine mitigated ETOH- and NIC + ETOH-induced deficits. Locomotor hyperactivity identified in ETOH and NIC + ETOH mice was ameliorated by vinpocetine. While cyclic nucleotides levels in cerebral cortex and hippocampus were reduced by NIC, ETOH and NIC + ETOH, this outcome was more consistent in the latter group. As observed for behavior, vinpocetine normalized NIC + ETOH nucleotides levels. pCREB levels were also increased in response to vinpocetine, with stronger effects in the NIC + ETOH group. Exposure to both drugs of abuse worsens behavioral and neurochemical disruption. These findings and the amelioration of deleterious effects by vinpocetine support the idea that cAMP and cGMP signaling contribute to nicotine- and ethanol-induced hyperactivity and memory/learning deficits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Reacción de Prevención / Encéfalo / AMP Cíclico / GMP Cíclico / Etanol / Hipercinesia / Nicotina Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: Neurotoxicology Año: 2018 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Efectos Tardíos de la Exposición Prenatal / Reacción de Prevención / Encéfalo / AMP Cíclico / GMP Cíclico / Etanol / Hipercinesia / Nicotina Tipo de estudio: Prognostic_studies Límite: Animals / Pregnancy Idioma: En Revista: Neurotoxicology Año: 2018 Tipo del documento: Article Pais de publicación: Países Bajos