*2.1. Animals*

Adult male Sprague Dawley rats (Charles River, Calco, Italy) weighing 280 to 300 g on arrival were housed in groups of 2 in standard polycarbonate cages under standard laboratory conditions of temperature (21 ± 1 ◦C), humidity (50–60%), and artificial light (from 07:00 to 19:00 h). [29]. All animal procedures were conducted at the Department of Pharmacological and Biomolecular Sciences at the University of Milan, and carried out in accordance with the principles set out in the following laws, regulations, and policies governing the care and use of laboratory animals: Italian Governing Law (D.lgs 26/2014; Authorization n.19/2008-A issued 6 March 2008, by Ministry of Health); the NIH Guide for the Care and Use of Laboratory Animals (2011 edition) [30]; and EU directives and guidelines (EEC Council Directive 2010/63/UE). All efforts were made to minimize animal suffering and to keep the lowest number of animals used. The experiments have been reported in compliance with the ARRIVE guidelines.
