Electrophysiological and neurochemical characterization of 7-nitroindazole and molsidomine acute and sub-chronic administration effects in the dopaminergic nigrostriatal system in rats

Arcangelo Benigno, Gergely Orban, Giuseppe Crescimanno, Giuseppe Di Giovanni, Ennio Esposito, Massimo Pierucci, Vincenzo Di Matteo, Arcangelo Benigno, Giuseppe Di Giovanni, Giuseppe Crescimanno

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16 Citazioni (Scopus)

Abstract

Nicotine, the main psychoactive ingredient in tobacco, stimulates dopamine (DA) function, increasing DA neuronal activity and DA release. DA is involved in both motor control and in the rewarding and reinforcing effects of nicotine; however, the complete understanding of its molecular mechanisms is yet to be attained. Substantial evidence indicates that the reinforcing properties of drugs of abuse, including nicotine, can be affected by the nitric oxide (NO) system, which may act by modulating central dopaminergic function. In this study, using single cell recordings in vivo coupled with microiontophoresis and microdialysis in freely moving animals, the role of NO signaling on the hyperactivation elicited by nicotine of the nigrostriatal system was investigated in rats. Nicotine induced a dose-dependent increase of the firing activity of the substantia nigra pars compacta (SNc) DA neurons and DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in the striatum. Pharmacological manipulation of the NO system did not produce any change under basal condition in terms of neuronal discharge and DA release. In contrast, pretreatments with two NO synthase (NOS) inhibitors, N-omega-nitro-l-arginine methyl ester (l-NAME) and 7-nitroindazole (7-NI) were both capable of blocking the nicotine-induced increase of SNc DA neuron activity and DA striatal levels. The effects of nicotine in l-NAME and 7-NI-pretreated rats were partially restored when rats were pretreated with the NO donor molsidomine. These results further support the evidence of an important role played by NO on modulation of dopaminergic function and drug addiction, thus revealing new pharmacological possibilities in the treatment of nicotine dependence and other DA dysfunctions.
Lingua originaleEnglish
Titolo della pubblicazione ospiteBirth, Life and Death of Dopaminergic Neurons in the Substantia Nigra
Pagine173-182
Numero di pagine10
Stato di pubblicazionePublished - 2009

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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