Diazepam-insensitive [3H]Ro 15-4513 binding in intact cultured cerebellar granule cells

A major QTL for acute ethanol sensitivity in the alcohol tolerant and non‐tolerant selected rat lines

“…After 7 generations of selection, the lines differed significantly in ataxic sensitivity, but not in ethanol metabolism or in blood acetaldehyde levels (Eriksson & Rusi 1981). The AT and ANT rats have been studied extensively, primarily by Korpi and colleagues (Hellevuo et al 1989; Hellevuo & Korpi 1988; Kaheinen et al 1988; Korpi & Uusi-Oukari 1989; Korpi et al 1992a; Korpi et al 1992b; Korpi et al 1992c; Makela et al 1995; Malminen & Korpi 1988; Malminen & Korpi 1989; Nakki et al 1995; Sarviharju & Korpi 1993; Tuominen & Korpi 1991; Uusi-Oukari & Korpi 1989; Uusi-Oukari & Korpi 1990; Uusi-Oukari & Korpi 1991; Uusi-Oukari & Korpi 1992). …”

Studies on the binding of [3H]flumazenil and [3H]sarmazenil in post‐mortem human brain

“…Consequently, as yet no selective radioligands exist for binding studies in vivo or in vitro for receptor characterization. However, by the The total as well as the non-specific binding was determined from the inhibition curves using the iterative nonlinear least-squares curve-fitting program LIGAND (Munson and Rodbard, 1980 GABA, which binds to the same receptor-ion channel complex, has different effects on the binding of the two radioligands used, related to their different intrinsic activities (Braestrup et al, 1983 (Malminiemi and Korpi, 1989) and in situ hybridization studies (Kato, 1990;Luddens et al, 1990) showing that a6-subunit containing receptors are present only in granule cells of the cerebellum.…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…The cause for these changes is not clear, but one possibility is that the putative primary reduction in a1 expression leaves the g2 subunit (that is needed for synaptic targeting) available to assemble with a4 subunits, which increases the synaptic a4 subunit-containing receptors. In these receptors, the inverse agonist of the benzodiazepine-site Ro 15-4513 acts as an agonist [like in a6 subunit-containing receptors of the cerebellar granule neurons (Malminiemi and Korpi, 1989)] and enhances the synaptic responses only in the ethanol-dependent rats . The CeA, a major component of the extended amygdala, has emerged as an important brain area for both the acute positive reinforcement of drugs of abuse and negative reinforcement associated with protracted abstinence.…”

“…This residue was originally detected in an "abnormal" subunit a6 (Luddens et Wieland et al, 1992), with restricted expression to cerebellar granule neurons. Receptors with this subunit do not bind diazepam but bind an inverse agonist imidazobenzodiazepine Ro 15-4513, correlating with the pharmacological profile of the cerebellar granule cell layer (Sieghart et al, 1987;Malminiemi and Korpi, 1989;Uusi-Oukari and Korpi, 1990;Turner et al, 1991). Furthermore, a spontaneous mutation changing arginine (Arg) to glutamine (Gln) was detected in the cerebellar a6 subunit of alcohol-sensitive, and particularly BZ-sensitive, ANT rat line reviewed in Korpi et al, 2007).…”