Opioids, benzodiazepines and intake of ethanol

Beaman, Carol M.; Hunter, George A.; Dunn, Laura L.; Reid, Larry D.

doi:10.1016/0741-8329(84)90034-x

Cited by 48 publications

(4 citation statements)

References 19 publications

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“…Previous reports have demonstrated that sarmazenil is approximately 5–15 times more potent as a BDZ antagonist than flumazenil in animals and man (Gath et al, 1984; Pieri, Biery, & Wdonwicki, 1985). Similar to the findings of the present study with sarmazenil, some reports have shown that low-to-moderate doses of flumazenil (1–10 mg/kg) do not alter EtOH intake (Beaman, Hunter, Dunn, & Reid, 1984; McBride et al, 1988). However, June, Hughes, et al(1994) demonstrated that a 16 mg/kg dose of flumazenil reliably reduced EtOH intake in stock rats, and a 40 mg/kg dose suppressed EtOH drinking in P rats (June et al, in press).…”

Section: Discussionsupporting

confidence: 91%

Effects of negative modulators of GABAergic efficacy on ethanol intake: Correlation of biochemical changes with pharmacological effect using a behavioral paradigm.

June¹,

Lin²,

Greene³

et al. 1995

Experimental and Clinical Psychopharmacology

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Negative allosteric modulators of varying intrinsic efficacies that reduce GABAergic function were evaluated for the ability to decrease the reinforcing properties of ethanol (EtOH) in the selectively bred alcohol-preferring (P) rats. Pretreatment with negative modulators maximally reduced EtOH intake during the initial 15-min interval to 9% to 49% of control levels; however, rank-order potencies of negative modulators to attenuate EtOH intake were not correlated with rank-order potencies of negative modulators to inhibit -/-ammo-butyric acid (GABA) 36 C1~ conductance and enhance 35 S-t-butylbicyclophosphorothionate (TBPS) binding. Thus, the underlying mechanism mediating inhibition of EtOH intake and inhibition of 36 C1~ conductance or enhanced TBPS ratios may not be identical. The ability of inverse agonists to modify the reinforcing actions of EtOH may be related to their affinity at different GABA A -benzodiazepine receptor subtypes.Considerable research has demonstrated that benzodiazepine (BDZ) inverse agonists [negative allosteric modulators of gamma-amino-butyric acid (GABAergic) efficacy] antagonize the actions of ethanol (EtOH) at both the behavioral (for review,

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Section: Discussionsupporting

confidence: 91%

Effects of negative modulators of GABAergic efficacy on ethanol intake: Correlation of biochemical changes with pharmacological effect using a behavioral paradigm.

June¹,

Lin²,

Greene³

et al. 1995

Experimental and Clinical Psychopharmacology

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“…Others (Beaman et al 1984), using a Iwobottle choice tcst between a sweetened EtOH solution Bcnzodiazepincs Alter Ethanol lnt.lke 63 and water in stock rats, found that chlordiazepoxide (3-12 mg/ kg) generally incrcaSL"'<i total fluid intake, but it did not alter the rats' propensity to self-admi nister EtOH. 5.1mson and Grant (1985), using a concu rrent scht.odule proa.>dure, demonstrated thot chlordiazepoxide generally reduced EtOH-reinforCf.od n. >spondi ng and intake.…”

Section: Discussionmentioning

confidence: 99%

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats

June

Murphy

Hewitt

et al. 1996

Neuropsychopharmacology

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Bellwtiiaul'illc (8DZ) rcecIJlar ligullds willi varyingIII/ril/sic efficacies FG 7142 Ident ifying both the env ironmental and biological variables that promote and maintain high alcohol-seeking or alcohol self-administration behavior is key to unders tanding the disorder of alcohol abuse and alcoholism (Li et al. 1991). Selective breed ing methodology has demonstrated convincingly thai there is genetic int1u-ence on alcohol-seeking beh.wior ( Li et aL 1991). Currently there are four pairs (high and low) of rat lines that differ in alcohol preference (Ericksson and Rusi 1981; Mardones and Segozia-Riq uelene 1983; Li ct a l.

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“…Bidirectional effects of opioid receptor ligands have been reported in many animal models of ethanol self-administration: low doses of µ-opioid agonists, such as morphine, increase alcohol drinking (Beaman et al 1984;Hubbell et al 1987), while non-selective opioid antagonists (naloxone, naltrexone, nalmefene; Altshuler et al 1980;Froehlich et al 1990;Weiss et al 1990;Hubbell et al 1991;Kornet et al 1991;Schwarz-Stevens et al 1992) and antagonists selective for µ-and δ-opioid receptors decrease alcohol intake both in rodents and primates (Froehlich et al 1991;Hyytiä 1993;Lê et al 1993;Krishnan-Sarin et al 1995a, 1995b. There is also evidence that a genetic disposition towards alcohol drinking may be accompanied both by altered basal levels of opioid peptides in the brain and an increased sensitivity of the endogenous opioid system to ethanol.…”

Section: Introductionmentioning

confidence: 99%

Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking

Hyytiä¹,

Ingman

Soini

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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Effects of a continuous naloxone infusion via osmotic pumps on alcohol drinking and opioid receptor density and function in the high-drinking AA (Alko, Alcohol) rats were examined. AA rats were trained to drink 10% (v/v) ethanol in a 1-h limited access procedure and implanted with subcutaneous osmotic pumps delivering either saline, a low dose (0.3 mg/kg per hour), or a high dose (3.0 mg/kg per hour) of naloxone for 7 days. The pumps were then removed and alcohol, food and water intakes were measured for another 4 days. Compared with saline, both naloxone doses significantly suppressed 1-h alcohol intake during the 7-day infusion. The suppression was smaller than that by a bolus injection of the same daily dose 15 min before the session, although a complete blockade of morphine-induced antinociception was achieved even with the smaller naloxone infusion. Significant decreases were also seen in daily food and water intake during the first days, but they quickly returned to their previous baselines. After pump removal, rats of both naloxone-treated groups rapidly increased their alcohol drinking and reached the pretreatment baseline, while their food and water intakes significantly surpassed their baselines. Naloxone infusion at 3.0 mg/kg per hour for 7 days significantly decreased 24-h alcohol drinking without affecting alcohol preference. Twenty-four hours after pump removal, autoradiography with [3H]DAMGO, [3H]DPDPE and [3H]U-69,543 revealed an up-regulation of mu-, delta- and kappa-opioid receptor binding sites in many brain areas of these animals. This receptor up-regulation was functional, because receptor coupling to G-protein activation was enhanced by agonist ligands, as revealed by [35S]GTPgammaS autoradiography. A good correlation existed between ligand binding densities and G-protein activation for mu- and kappa-receptors in control and naloxone-treated brain sections. Furthermore, morphine-induced analgesia in a hot-plate test showed a leftward shift in the morphine dose-response curve after naloxone treatment. These results suggest that the usefulness of a chronic opioid antagonist dosing regime could be limited by nonspecific effects of the antagonist on ingestive behaviour, an up-regulation of opioid receptors with high antagonist doses, and the resulting supersensitivity to opioid agonists after the discontinuation of the treatment.

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Opioids, benzodiazepines and intake of ethanol

Cited by 48 publications

References 19 publications

Effects of negative modulators of GABAergic efficacy on ethanol intake: Correlation of biochemical changes with pharmacological effect using a behavioral paradigm.

Effects of negative modulators of GABAergic efficacy on ethanol intake: Correlation of biochemical changes with pharmacological effect using a behavioral paradigm.

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats

Effects of continuous opioid receptor blockade on alcohol intake and up-regulation of opioid receptor subtype signalling in a genetic model of high alcohol drinking

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