As discussed for alcohol, several preclinical studies have demonstrated that dysregulation of astrocyte function, particularly as it relates to glutamate homeostasis, is a common neuroimmune response for other drugs of abuse. For example, chronic opioid or stimulant use decreases astrocytic expression of GLT-1 (Ozawa et al., 2001; Shen et al., 2014) (Althobaiti et al., 2016; Knackstedt et al., 2010). In rats, GLT-1 gene transfer in the NAc shell reduces morphine- and methamphetamine-induced CPP (Fujio et al., 2005), while gene transfer in the locus coeruleus reduces morphine dependence (Ozawa et al., 2004). Ceftriaxone and N-acetylcysteine both help restore GLT-1 expression in astrocytes, which may be related to their anti-inflammatory properties (Lasram et al., 2014; Wei et al., 2012). Treatment with these compounds decreases morphine dependence, tolerance (Habibi-Asl et al., 2014), and relapse in preclinical models (Shen et al., 2014). However, ceftriaxone requires intravenous administration and has poor brain penetrability, limiting its potential clinical use. Alternatively, clavulanic acid can be used to increase GLT-1 expression, and it reduces cocaine’s reinforcing effects (Kim et al., 2015) and the rewarding properties of opioids in
