Effects of γ-hydroxybutyric acid and flunitrazepam on ethanol intake in male rats

Leonard, Stuart T.; Gerak, Lisa R.; Gurkovskaya, Olga V.; Moerschbaecher, Joseph M.; Winsauer, Peter J.

doi:10.1016/j.pbb.2006.11.013

Cited by 7 publications

(13 citation statements)

References 43 publications

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“…In contrast to previous studies of DHEA in this laboratory that utilized a limited-access two-bottle choice test (Gurkovskaya et al ., 2009; Leonard et al ., 2006; Worrel et al ., 2011), rats were trained under a multiple FR-20, FR-10 schedule maintained by both food and ethanol presentation to assess the effects of ethanol, DHEA, 7-keto DHEA, chlordiazepoxide, rauwolscine, and RO15-4513 on ethanol intake. Responding for ethanol under this multiple schedule produced BECs similar to, or higher than, many binge studies utilizing operant self-administration, home-cage two-bottle choice procedures, or non-contingent ethanol infusion (Ji et al , 2008; Prasad et al , 2001; Schulteis et al , 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Subjects were trained to consume ethanol orally using a modified saccharin-fading procedure (Leonard et al , 2006; Samson, 1986). Prior to each daily training session, subjects were weighed and then placed in an illuminated operant chamber where each subject had access to a 50-ml plastic centrifuge tube, which contained a saccharin/ethanol solution.…”

Section: Methodsmentioning

confidence: 99%

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A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Amato¹,

Hulin²,

Winsauer³

2012

Behavioural Pharmacology

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Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol- and food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Amato¹,

Hulin²,

Winsauer³

2012

Behavioural Pharmacology

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“…However, investigations of this possibility have yielded seemingly equivocal findings, at least in terms of ethanol consumption. For instance, studies have reported that BZ treatment increases (Petry, 1995; Petry, 1997; Sawyer et al, 2014; Schmitt et al, 2002; Soderpalm and Hansen, 1998; Winger et al, 2007), decreases (Chan et al, 1983a,b; Roehrs et al, 1984; Samson and Grant, 1985), or has no effect (Barrett and Weinberg, 1975; Leonard et al, 2006; Rimondini et al, 2002; Roehrs et al, 1984) on measures of ethanol consumption. However, the reinforcing effects of the BZ in isolation were only assessed in the study of Winger et al (2007), so the other reports were unable to compare the relative reinforcing effects of the mixture to that of each of its components (i.e., both the BZ and ethanol).…”

Section: Introductionmentioning

confidence: 99%

Reinforcing effectiveness of midazolam, ethanol, and sucrose: behavioral economic comparison of a mixture relative to its component solutions

Townsend

Platt²,

Rowlett³

et al. 2017

Behavioural Pharmacology

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Benzodiazepines (BZs) are relatively safe when administered alone. However, these drugs can produce severe side effects when co-administered with ethanol. Despite these adverse consequences, rates of concurrent BZ and ethanol misuse are increasing, and it is unclear if this behavior is maintained by an enhanced reinforcing effect of the mixture. To address this issue, the current study compared the reinforcing effectiveness of sucrose solutions mixed with midazolam, ethanol, or both. Eight male rats were trained to orally self-administer solutions of either sucrose (S), sucrose + midazolam (SM), sucrose + ethanol (SE), or sucrose + midazolam + ethanol (SME). The response requirement was increased between sessions until the number of reinforcers earned was zero, and the relationship between response requirement and reinforcers earned was analyzed using the behavioral economic approach of exponential model of demand. Baseline intake was similar across drug conditions. Consumption of SM was least affected by increases in cost, indicating it possessed the highest reinforcing effectiveness (i.e., least elastic). The reinforcing effectiveness of S, SE, and SME did not differ significantly. The fact that the reinforcing effectiveness of the SME was less than that of SM does not support the supposition that BZ and ethanol co-administration is maintained by a higher reinforcing effectiveness of the mixture.

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“…In general, these two epimers have been shown to increase ethanol intake at intermediate doses, while decreasing intake at higher doses in both rats and mice. However, these effects likely depend on a number of pharmacological and behavioral variables, and they are not consistently produced by all of the different types of positive GABA A receptor modulators (e.g., Amato et al, 2012; Janak, Redfern, & Samson, 1998; Leonard, Gerak, Gurkovskaya, Moerschbaecher, & Winsauer, 2006). With respect to the pregnane steroids, for example, intermediate doses of pregnanolone did not increase operant responding for ethanol in the present study involving rats, but intermediate doses of allopregnanolone did increase operant responding for ethanol after both i.p.…”

Section: Discussionmentioning

confidence: 99%

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats

Hulin

Lawrence

Amato

et al. 2015

Alcohol

Self Cite

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The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under an FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding, whereas the reverse was true for naltrexone. Acamprosate decreased responding for both reinforcers with equal potency. In Experiment 2, different mean intervals of food presentation significantly affected the number of food reinforcers obtained per session; however, changes in the number of food reinforcements did not significantly affect responding for ethanol. Under the FR-10 VI-80 schedule in Experiment 3, only naltrexone significantly decreased both the dose of alcohol presented and blood ethanol concentration (BEC). Acamprosate and pregnanolone had no significant effects on any of the dependent measures, whereas DHEA significantly decreased BEC, but did not significantly decrease response rate or the dose presented. In summary, DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained responding under a multiple FR-10 FR-20 schedule, and were more selective for decreasing ethanol self-administration than either naltrexone or acamprosate under that schedule. Experiment 2 showed that ethanol intake was relatively independent of the density of reinforcement in the food-maintained component, and Experiment 3 showed that naltrexone was the most effective drug at the doses tested when the density for food reinforcement was low and maintained under a variable-interval schedule.

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Effects of γ-hydroxybutyric acid and flunitrazepam on ethanol intake in male rats

Cited by 7 publications

References 43 publications

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule

Reinforcing effectiveness of midazolam, ethanol, and sucrose: behavioral economic comparison of a mixture relative to its component solutions

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats

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