Benzodiazepines enhance the consumption and palatability of alcohol in the rat

Abstract

This study examined the effect of the benzodiazepine, midazolam, on the consumption and palatability of 6% ethanol in male Wistar rats. In the first experiment, it was found that midazolam (5 mg/kg) increased home cage ethanol drinking 0-2 h after administration. Another intake experiment, in which ethanol was infused directly into the oral cavity through an indwelling catheter, also showed that midazolam (10 mg/kg) stimulated alcohol ingestion. The affective response to intraoral infusions of ethanol (1 ml during 1 min) was subsequently monitored in benzodiazepine-treated rats. Taste reactivity testing showed that midazolam (5-10 mg/kg) significantly increased the occurrence of hedonic orofacial responses and suppressed the number of passive drippings. A similar response pattern was observed following administration of diazepam (5 mg/kg) and chlordiazepoxide (10 mg/kg), but not after exposure to cis(Z)flupentixol (10 mg/kg). Midazolam also increased the incidence of hedonic responses in alcohol-naive rats with no previous access to ethanol in the home cages. Hedonic responsiveness did not appear to diminish with repeated benzodiazepine exposure: the behaviour of rats given five midazolam injections (10 mg/kg every second day) was similar to that shown by rats with no benzodiazepine pre-exposure. The increased hedonic response to ethanol induced by midazolam was blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil (10 mg/kg), the latter drug exerting no effects on its own. The present results suggest that benzodiazepines, by acting on GABA(A) receptors, may facilitate ethanol intake by increasing ethanol's taste hedonic properties.

α1-noradrenergic receptor antagonism blocks dependence-induced increases in responding for ethanol

“…Consistent with this hypothesis is the observation that classical anxiolytics (e.g., benzodiazepines) have the ability to increase non-dependent ethanol self-administration (Soderpalm and Hansen, 1998) and the same dose (0.25 mg/kg) of prazosin was able to attenuate the anxiogenic effects of nicotine administration in the elevated plus-maze (Zarrindast et al, 2000). An alternative explanation for the selective increases in self-administration observed in nondependent animals is that the low dose of prazosin is by some method increasing stress and thereby causing increased self-administration.…”

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.…”

Chronic Ethanol Potentiates the Effect of Neuropeptide S in the Basolateral Amygdala and Shows Increased Anxiolytic and Anti-Depressive Effects

“…They may, therefore, be subject to abusive use or reinforce drug-seeking behaviors in alcoholics (Soderpalm and Hansen, 1998;Schmitt et al, 2002;Isbister et al, 2004;O'Brien C, 2005). Our data indicate that NPS alleviates anxiety and depression at doses that do not elicit CPP, but nevertheless actually reduce EtOH consumption.…”

“…BZDs, in turn, are themselves habit-forming. Importantly, BZDs have also been shown to increase the palatability of EtOH and increase alcohol consumption (Soderpalm and Hansen, 1998). Thus, there is a significant need for novel targets and treatments for anxiety disorders, especially for anxiety that is co-morbid with alcoholism.…”