The DID paradigm has been used in several laboratories to explore pharmacological control of this novel drinking paradigm. To date, most such studies have employed peripheral administration of compounds to C57BL/6J mice, typically before the second day of DID testing. Studies have shown that the mu opioid antagonist naltrexone and the dopamine transporter antagonist GBR 12909 both reduced DID intake of ethanol at doses without effect on intake of plain water (Kamdar et al. 2007). GBR, but not naltrexone, also reduced sweetened water intake. A subsequent study showed that acamprosate, which blocks NMDA and/or metabotropic glutamate receptors, and the specific mGluR5 receptor antagonist MPEP both reduced DID ethanol drinking. Neither compound affected water or sugar water drinking at the doses tested (Gupta et al. 2008). The GABA-B agonist baclofen dose-dependently increased binge-like ethanol intake, without affecting water drinking, while both the GABA-A agonists muscimol and THIP reduced ethanol intake, but also water (Moore et al. 2007). Nicotinic acetylcholine receptor function may also be involved as shown in a recent study using mecamylamine, hexamethonium, dihydro-beta-erythroidine (DHβE), methyllycaconitine (MLA), nicotine and cytisine
