Drug effects on multiple and concurrent schedules of ethanol‐ and food‐maintained behaviour: context‐dependent selectivity

Abstract

BACKGROUND AND PURPOSEDrugs that more potently or effectively reduce ethanol-maintained behaviour versus an alternative are considered selective and are considered promising pharmacotherapies for alcoholism. Such results are often obtained using separate groups or multiple schedules where ethanol and the alternative are available alone or sequentially. Recently, we observed that when ethanol and food were available sequentially under a multiple schedule, fluvoxamine and varenicline were selective; yet this selectivity disappeared when ethanol and food were concurrently available. EXPERIMENTAL APPROACHWe examined the generality of these findings by comparing doses of several drugs required to decrease ethanol-and food-maintained responding under a multiple schedule and under a concurrent schedule. Effects were determined for chlordiazepoxide, 2,5-dimethoxy-4-iodoamphetamine (DOI), meta-chlorophenylpiperazine (mCPP), morphine, naltrexone and d-amphetamine. KEY RESULTSUnder the multiple schedule, ED50 values for decreases in ethanol-maintained responding were significantly different and lower than ED50s for decreases in food-maintained responding (demonstrating selectivity) for each drug except for chlordiazepoxide (which was equipotent) and naltrexone (which did not affect responding). However, this selectivity vanished or even inverted under the concurrent schedule, such that ED50 values for decreasing ethanol-and food-maintained responding were not different (or, following DOI, the ED50 for food-maintained responding was lower than for ethanol-maintained responding). CONCLUSIONS AND IMPLICATIONSResults are consistent with those seen following fluvoxamine and varenicline administration, and suggest that selectivity is assay-dependent. These results indicate the need for careful interpretation of selective drug effects, especially when obtained in situations where ethanol or the alternative is the only programmed reinforcement available.Abbreviations 5-HT, 5-hydroxytryptamine; DOI, 2,5-dimethoxy-4-iodoamphetamine; IQR, interquartile range; mCPP, meta-chlorophenylpiperazine

Determinants of choice, and vulnerability and recovery in addiction

“…In this case, several strategies for reducing drug choice are apparent. First, one could reduce the effectiveness of drug at reinforcing behavior, and several pre-clinical studies have used choice procedures to study medications that might attenuate drug reinforcement (Ginsburg & Lamb 2014; Negus 2005; Weiss et al 1990). Another commonly used clinical strategy is the differential reinforcement of other behavior (DRO), i.e ., reinforcing the non-occurrence of drug use.…”

Varenicline and GZ-793A differentially decrease methamphetamine self-administration under a multiple schedule of reinforcement in rats

“…Future studies using the current multiple schedule may be able to better control for differences in reinforcer density by increasing the ratio value for the food or potentially by shortening the length of the components. Previous research by Ginsburg and Lamb (2014a,b) using a multiple schedule of oral ethanol and food found that reinforcer density between the two reinforcers could be equated by shortening the components to 5 minutes.…”

“…Finally, another limitation in the current study may be that use of a multiple schedule may overestimate the selectivity of a potential pharmacotherapy. Research by Ginsburg and Lamb ( 2014a,b) found that varenicline and other drugs showed selectivity in decreasing ethanol intake under a multiple schedule of ethanol and food, but this selectivity was decreased or reversed when ethanol and food were available concurrently. It is possible that the selectivity seen in GZ-793A may be due to the use of a multiple schedule, although previous research using group designs also showed selectivity.…”

Alcohol abuse and related disorders treatment of alcohol dependence

“…Предполагается, что фармакологическое действие акампросата как антагониста NMDA-рецепторов (и, воз-можно, частичного агониста ГАМКА-рецепторов) заключа-ется в восстановлении баланса между нейротрансмиссией ГАМК и глутамата, измененного при злоупотреблении ал-коголем [8][9][10].…”