Table 3.

Effects of Glial Modulators on the Abuse Potential of Alcohol

Preclinical Studies
Glial Modulator	Mechanism of Action	Dose	Behavioral Outcome	Result	Citation
Indomethacin	Cyclooxygenase-1&2 Inhibitor	1.9, 2.5 & 5 mg/kg	Reinforcing Effects	↓	George, 1989
Rolipram	Selective Phosphodiesterase-4 (PDE-4) Inhibitor	0.25 & 0.5 mg/kg	Reinforcing Effects	↓	Hu et al., 2011
		0.1 & 0.2 mg/kg	Reinforcing Effects	↓	Wen et al., 2012
		1 mg/kg	Reinforcing Effects	↓	Blednov et al., 2014
CDP840	Selective PDE-4 Inhibitor	10 & 25 mg/kg	Reinforcing Effects	↓
Mesopram	Selective PDE-4 Inhibitor	5 mg/kg	Reinforcing Effects	↓
Piclamilast	Selective PDE-4 Inhibitor	1 mg/kg	Reinforcing Effects	↓
Propentofylline	PDE Inhibitor & Glutamate Transporter-1 (GLT-1) Upregulator	5 mg/kg	Reinforcing Effects	--
Various	PDE-1,3,5 and Non-specific Inhibitors	--	Reinforcing Effects	--
Ibudilast	PDE & Tumor Necrosis Factor-Alpha (TNF-α)	3,6 & 9 mg/kg	Reinforcing Effects	↓	Bell et al., 2015
Minocycline	Tetracycline Antibiotic & Microglial Inhibitor	50 mg/kg	Reinforcing Effects	↓	Agrawal et al., 2011
		60 & 80 mg/kg	Reinforcing Effects	↓	Syapin et al., 2016
Rapamycin	T-Lymphocyte & Astrocyte Inhibitor	50 & 100 ng/side	Reinforcing Effects	↓	Cozzoli et al., 2016
Tigecycline	Glycylcycline Antibiotic & Microglial Inhibitor	40, 60, 80 & 100 mg/kg	Reinforcing Effects	↓	Bergeson et al., 2016
		60 & 80 mg/kg	Reinforcing Effects	↓	Syapin et al., 2016
		80 mg/kg	Withdrawal	↓	Martinez et al., 2016
Ceftriaxone	Cephalosporin Antibiotic & Upregulator of GLT-1 and Cystine/Glutamate Antiporter (xCT)	100 mg/kg	Reinforcing Effects	↓	Alhaddad et al., 2014
		100 mg/kg	Reinforcing Effects	↓	Das et al., 2015
		100 mg/kg	Reinforcing Effects	↓	Sari et al., 2014
		200 mg/kg	Reinforcing Effects	↓	Sari et al., 2016
		50 & 100 mg/kg	Reinforcing Effects & Reinstatement of Drug Seeking	↓	Qrunfleh et al., 2013
		200 mg/kg	Reinstatement of Drug Seeking	↓	Rao and Sari, 2014
		100 mg/kg	Reinstatement of Drug Seeking	↓	Weiland et al., 2015
		200 mg/kg	Reinforcing Effects	↓	Lee et al., 2013
(+)-Naloxone	Non-Opioid Isomer of the Opioid Receptor Antagonist & Toll-Like Receptor-4 (TLR-4) Antagonist	30 & 60 mg/kg	Reinforcing Effects	--	Harris et al., 2017
Pioglitazone	Peroxisome Proliferator-Activated Receptor-Gamma (PPARγ) Activator & Cytokine Inhibitor	30 mg/kg	Reinstatement of Drug Seeking	↓	Blednov et al., 2015
		10 & 30 mg/kg	Reinstatement of Drug Seeking	↓	Stopponi et al., 2013
Clinical Studies
Glial Modulator	Mechanism of Action	Dose	Behavioral Outcome	Result	Citation
Ibudilast	PDE & TNF-α Inhibitor	50 mg	Positive Subjective Effects	--	Ray et al., 2017
		50 mg	Craving	↓
Minocycline	Tetracycline Antibiotic & Microglial Inhibitor	100 & 200 mg	Positive Subjective Effects	--	Petrakis et al., 2019