Nazzareno Cannella1, Marsida Kallupi1, Hong Wu Li1, Serena Stopponi1, Carlo Cifani1, Roberto Ciccocioppo1, Massimo Ubaldi2. 1. School of Pharmacy, Pharmacology Unit, University of Camerino, Building of Experimental Medicine, Via Madonna delle Carceri 9, Camerino, MC, 62032, Italy. 2. School of Pharmacy, Pharmacology Unit, University of Camerino, Building of Experimental Medicine, Via Madonna delle Carceri 9, Camerino, MC, 62032, Italy. massimo.ubaldi@unicam.it.
Abstract
RATIONALE: Neuropeptide S (NPS) displays unique pharmacological properties and induces both anxiolytic and pro-stress/arousal activities. Previous studies performed using Wistar rats demonstrated that NPS facilitated alcohol and cocaine seeking but did not affect alcohol or cocaine consumption. OBJECTIVES: Here, we investigated the effects of NPS in Marchigian Sardinian alcohol-preferring (msP) rats, a rat strain characterized by excessive alcohol consumption comorbid with heightened anxiety and depressive-like phenotypes. Specifically, we evaluated the effect of NPS on operant alcohol self-administration by msP rats compared to Wistar rats. The effect of NPS on cue-induced reinstatement of alcohol seeking in msP rats was also evaluated. Finally, using the open field test (OFT) and the elevated plus maze (EPM), we evaluated the effects of NPS on locomotor activity and anxiety. RESULTS: NPS reduced alcohol self-administration but did not affect cue-induced reinstatement in the msP rat. In addition, NPS induced reinstatement of extinguished alcohol seeking in Wistar rats without affecting alcohol intake. In the EPM task, NPS, in accordance with its anxiolytic activity, increased the time spent in the open arm of the arena by msP rats, although this effect was not observed in Wistar rats. CONCLUSIONS: These data suggest that the effect of NPS is strongly influenced by the genetic background of the animal. In Wistar rats, NPS acts as a pro-arousal agent to promote the reinstatement of alcohol seeking. However, when alcohol drinking is motivated by or associated with a state of pathological anxiety, NPS attenuates alcohol consumption and seeking due to its anxiolytic activity.
RATIONALE: Neuropeptide S (NPS) displays unique pharmacological properties and induces both anxiolytic and pro-stress/arousal activities. Previous studies performed using Wistar rats demonstrated that NPS facilitated alcohol and cocaine seeking but did not affect alcohol or cocaine consumption. OBJECTIVES: Here, we investigated the effects of NPS in Marchigian Sardinian alcohol-preferring (msP) rats, a rat strain characterized by excessive alcohol consumption comorbid with heightened anxiety and depressive-like phenotypes. Specifically, we evaluated the effect of NPS on operant alcohol self-administration by msP rats compared to Wistar rats. The effect of NPS on cue-induced reinstatement of alcohol seeking in msP rats was also evaluated. Finally, using the open field test (OFT) and the elevated plus maze (EPM), we evaluated the effects of NPS on locomotor activity and anxiety. RESULTS:NPS reduced alcohol self-administration but did not affect cue-induced reinstatement in the msP rat. In addition, NPS induced reinstatement of extinguished alcohol seeking in Wistar rats without affecting alcohol intake. In the EPM task, NPS, in accordance with its anxiolytic activity, increased the time spent in the open arm of the arena by msP rats, although this effect was not observed in Wistar rats. CONCLUSIONS: These data suggest that the effect of NPS is strongly influenced by the genetic background of the animal. In Wistar rats, NPS acts as a pro-arousal agent to promote the reinstatement of alcohol seeking. However, when alcohol drinking is motivated by or associated with a state of pathological anxiety, NPS attenuates alcohol consumption and seeking due to its anxiolytic activity.
Authors: A Rizzi; R Vergura; G Marzola; C Ruzza; R Guerrini; S Salvadori; D Regoli; G Calo Journal: Br J Pharmacol Date: 2008-03-31 Impact factor: 8.739
Authors: A Bifone; A Gozzi; A Cippitelli; A Matzeu; E Domi; H Li; G Scuppa; N Cannella; M Ubaldi; F Weiss; R Ciccocioppo Journal: Addict Biol Date: 2018-10-17 Impact factor: 4.280
Authors: Paola Palombo; Rodrigo M Leao; Paula C Bianchi; Paulo E C de Oliveira; Cleopatra da Silva Planeta; Fábio C Cruz Journal: Front Pharmacol Date: 2017-10-17 Impact factor: 5.810
Authors: Luca Botticelli; Emanuela Micioni Di Bonaventura; Massimo Ubaldi; Roberto Ciccocioppo; Carlo Cifani; Maria Vittoria Micioni Di Bonaventura Journal: Pharmaceuticals (Basel) Date: 2021-03-26
Authors: Nazzareno Cannella; Anna Maria Borruto; Michele Petrella; Maria Vittoria Micioni Di Bonaventura; Laura Soverchia; Carlo Cifani; Sara De Carlo; Esi Domi; Massimo Ubaldi Journal: Pharmaceuticals (Basel) Date: 2022-06-27