| Autor: |
Artur de la Villarmois E; Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina., Gabach LA; Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina., Bianconi S; Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.; INICSA-CONICET, Instituto de Fisiología, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina., Poretti MB; Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.; INICSA-CONICET, Instituto de Fisiología, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina., Occhieppo V; Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina., Schiöth HB; Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden., Carlini VP; Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.; INICSA-CONICET, Instituto de Fisiología, Facultad de Ciencias Médicas, UNC, Córdoba, Argentina., Pérez MF; Facultad de Ciencias Químicas, Departamento de Farmacología, IFEC-CONICET, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, 5000, Córdoba, Argentina. mfperez@fcq.unc.edu.ar. |
| Abstrakt: |
Behavioral sensitization to psychostimulants hyperlocomotor effect is a useful model of addiction and craving. Particularly, cocaine sensitization in rats enhanced synaptic plasticity within the hippocampus, an important brain region for the associative learning processes underlying drug addiction. Nitric oxide (NO) is a neurotransmitter involved in both, hippocampal synaptic plasticity and cocaine sensitization. It has been previously demonstrated a key role of NOS-1/NO/sGC/cGMP signaling pathway in the development of cocaine sensitization and in the associated enhancement of hippocampal synaptic plasticity. The aim of the present investigation was to determine whether NOS-1 inhibition after development of cocaine sensitization was able to reverse it, and to characterize the involvement of the hippocampus in this phenomenon. Male Wistar rats were administered only with cocaine (15 mg/kg/day i.p.) for 5 days. Then, animals received 7-nitroindazole (NOS-1 inhibitor) either systemically for the next 5 days or a single intra-hippocampal administration. Development of sensitization and its expression after withdrawal were tested, as well as threshold for long-term potentiation in hippocampus, NOS-1, and CREB protein levels and gene expression. The results showed that NOS-1 protein levels and gene expression were increased only in sensitized animals as well as CREB gene expression. NOS-1 inhibition after sensitization reversed behavioral expression and the highest level of hippocampal synaptic plasticity. In conclusion, NO signaling within the hippocampus is critical for the development and expression of cocaine sensitization. Therefore, NOS-1 inhibition or NO signaling pathways interferences during short-term withdrawal after repeated cocaine administration may represent plausible pharmacological targets to prevent or reduce susceptibility to relapse. |
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