Methamphetamine hydrochloride meth

Methamphetamine hydrochloride (METH) was purchased from Sigma-Aldrich (St. Louis, MO). Troriluzole mono hydrochloride monohydrate was designed and synthesized by Dr. Allen Reitz (Fox Chase Chemical Diversity Center, Doylestown, PA) as described (Pelletier et al., 2018 (link)), and shown in Fig. 1. All drugs were dissolved in physiological saline and injected intraperitoneally (IP) in a volume of 1 ml/kg. Doses of METH (0.5–1 mg/kg) were selected based on studies showing robust rewarding and locomotor stimulant effects in rats (Hofford et al., 2014 (link)). The dose range of TRLZ (1–16 mg/kg) was based on studies with RLZ (Sepulveda-Orengo et al., 2017), including adjustments for molecular weight differences between TRLZ (prodrug) and the parent compound (RLZ) (i.e., the molecular weight of TRLZ is approximately 2-fold greater than RLZ, so a dose of 8 mg/kg approximates a 4 mg/kg of RLZ).

(+)-Methamphetamine hydrochloride (meth) was obtained from Sigma Aldrich (St. Louis, MO, USA), dissolved in saline (0.9% NaCl) to 0.4 mg/ml concentration and used for intravenous self-administration. MK-801 ((5R,10S)-(+)-5-methyl-10,11-dihydro-5H dibenzo [a,d] cyclohepten-5,10-imine hydrogen maleate; Sigma-Aldrich, Czech Republic), was dissolved in saline and administered intraperitoneally (IP) at 0.3 mg/kg dose (1 ml/kg b.w.). Phencyclidine (1-(1-Phenylcyclohexyl) piperidine; Sigma-Aldrich, Czech Republic) was dissolved in saline and administered IP at 5 mg/kg dose (1 ml/kg b.w.). The control animals self-administered saline (meth rat controls) or received equivalent volumes of IP saline (MK-801 and PCP controls). The doses of each drug were based on previously published studies (Jentsch et al., 1997 (link); Li et al., 2011 (link); Schwendt et al., 2012 ; Stefani and Moghaddam, 2002 (link); Vales et al., 2006 (link)).