GABAA-benzodiazepine receptors in the striatum are involved in the sedation produced by a moderate, but not an intoxicating ethanol dose in outbred Wistar rats

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). However, as in the present study, RY008 was not effective in blocking the sedation produced by the 0.75 g/ kg dose.…”

“…Thus, we propose this precludes a "subtractive hypothesis" in explaining the attenuation of alcohol's action in the open field. Second, systemic injections of BDZ inverse agonists appear to be more effective in attenuating, but not reversing the EtOH sedation produce by doses >1.25 g/kg (June et al 1998d). Third, in the open field, partial and full BDZ inverse agonists (e.g.…”

“…These effects include EtOH's euphoric (McBride and Li 1998;June et al 2001), motor impairing, sedative (Draski and Deitrich 1996;June et al 1998d, and anxiolytic (Liljequist and Engel 1984;Koob et al 1986;June et al 1998b) actions. Most studies have employed negative GABAergic modulators such as benzodiazepine (BDZ) inverse agonists and competitive GABA antagonists to implicate GABA in EtOH's actions (for review, see Jackson and Nutt 1995;also Draski and Deitrich 1996).…”

Dopamine and Benzodiazepine-Dependent Mechanisms Regulate the EtOH-Enhanced Locomotor Stimulation in the GABAA α1 Subunit Null Mutant Mice

“…These data contrast recent and previous reports (June et al, 1998a, b) demonstrating that bCCt and other prototype BDZ antagonists (eg, ZK 93246, CGS 8216) were effective in attenuating the sedative actions of alcohol in rats. However, in these prior studies, a 1.25-1.50 g/kg dose of EtOH was employed (June et al, 1998a(June et al, , b, 2003. Thus, it is possible that while sedative EtOH doses can effectively be antagonized by BDZ receptor antagonists, higher EtOH doses (X3 g/kg), which effect multiple neurotransmitter systems (Draski and Deitrich, 1996), are not capable of being antagonized via BDZ ligands.…”

GABAA/α1 receptor agonists and antagonists: effects on species-typical and heightened aggressive behavior after alcohol self-administration in mice

“…Like b-CCt, 3-propoxy-b-carboline hydrochloride (3-PBC), a low-efficacy ligand with preferential action at receptors containing the a 1 subunit, suppresses alcohol-reinforced responding after central (i.e., anterior and medial ventral pallidum) and parenteral administrations. By contrast, flumazenil failed to reduce alcohol-reinforced responding after either parenteral or central injections (June et al 1998). The failure to reduce the alcohol-motivated responding by flumazenil may be due to its partial agonist activity at some a x b 3 g 2 receptors.…”