The novel benzodiazepine inverse agonist RO19-4603 antagonizes ethanol motivated behaviors: neuropharmacological studies

Reinstatement of ethanol and sucrose seeking by the neurosteroid allopregnanolone in C57BL/6 mice

“…The results indicated that a priming dose of the GABAergic neurosteroid ALLO or exposure to a CS previously paired with reinforcer delivery reinstated ethanol-seeking and sucrose-seeking behavior in mice. The majority of evidence supporting GABAergic involvement in the regulatory processes governing ethanol intake (Rassnick et al, 1993; Hodge et al, 1995, 1996; Hyytiä and Koob, 1995; Petry, 1997; Shelton and Balster, 1997; Janak et al, 1998; June et al, 1998a, 1998b; Nowak et al, 1998; Soderpalm and Hansen, 1998; Samson and Chappell, 2001; Sinnott et al, 2002b; Janak and Gill, 2003; Ford et al, 2005a, 2005b, 2007b; Krystal et al, 2006) indicate a relatively selective effect of GABA A receptor ligands on ethanol consumption, although benzodiazepines also have been reported to alter saccharin and food consumption in rats (e.g., Wegelius et al, 1994; Shelton and Balster, 1997). Collectively, the present findings in mice support a role of GABAergic neurosteroids such as ALLO in general motivation.…”

Intake of saccharin, salt, and ethanol solutions is increased by infusion of a mu opioid agonist into the nucleus accumbens

“…A further important consideration is that in the sucrose fading procedure, the ethanol taste may become a positive conditional stimulus (CS + ) after repeated pairings with sucrose; if this is the case, opioids could act to enhance the hedonic properties of the CS + . Finally it is also important to note that in addition to opioids, other neurotransmitter systems within the nucleus accumbens, particularly GABAergic (Heibreder and De Witte 1993;Hodge et al 1995;Hodge and Alken 1996;June et al 1998); and dopaminergic (Levy et al 1991;Samson and Hodge 1993;Samson et al 1999;Kaczmarek and Keifer 2000) systems may also play a critical role in the overall control of alcohol intake.…”

A high affinity ligand for GABA A -receptor containing a 5 subunit antagonizes ethanol?s neurobehavioral effects in Long-Evans rats

“…Ro15-4513, RY008) to antagonize the sedative effects of EtOH on the rotorod (Dar 1992;Meng and Dar 1994), and open field (June et al 1998a). In our previous study, systemic injections of RY008 (5 mg and 10 mg) (a structurally related inverse agonist) also antagonized the sedation produced by the 1.25 g/kg EtOH doses (June et al 1998d).…”

“…Behavioral testing was conducted in 15 standard operant conditioning chambers (Coulbourn Instruments) equipped with two removable levers and two dipper fluid delivery systems enclosed in sound-attenuated cubicles (see June et al 1998aJune et al , 1998bJune et al , 1998c. A green cue light above each lever was used to indicate the presence of a reinforcer.…”

“…The procedures have been described previously (for review, see June et al 1998aJune et al , 1998cJune 2002). After a period of stabilization on the concurrent FR1 schedule for pure EtOH (10% v/v) on both levers, water was then substituted in the dipper delivery system for one of the two levers.…”