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

Abstract

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.

Textile-based wearable device for detection of date rape drugs in drinks

“…The most drastic difference is between NaCl and the other two substances, at the same concentration. Our findings are similar to those reported in Townsend et al 32 as mixtures of sucrose and alcohol, as well as diazepam and alcohol, do not differ significantly when non-specific techniques are used. To see the relationship between the imaginary and real part of the impedance, as an indicator of a linear time-invariant system, Nyquist plots have been calculated.…”

Midazolam, methamphetamine, morphine and nicotine intake in high‐drinking‐in‐the‐dark mice

“…Unfortunately, the limited number of studies that have evaluated voluntary midazolam intake either have been undertaken in rats 27,57 or have not reported levels of midazolam intake, 58 precluding our ability to compare midazolam intake in HDID mice to those of other mouse strains. The range of midazolam intake observed in Experiment 1 (2-4 mg/kg), however, is equal to or greater than doses that were shown to produce anxiolysis in mice, 46 suggesting that HDID mice may be consuming enough midazolam to produce behavioural effects.…”

“…Here, we examine the voluntary intake patterns of midazolam, methamphetamine, morphine and nicotine in HDID mice for one drinking paradigm, DID: that is, the drinking task in which they drink binge‐like amounts of ethanol, sufficient to reach intoxication. These drugs were selected because each has high addiction potential in clinical populations, they are ingested orally by mice 23–26 and oral ingestion of these drugs has been shown to be reinforcing 27–30 . Further, the use of each of these drugs has demonstrated potentiation of alcohol intake, 31–34 and the use of these drugs has been shown to be potentiated by an alcohol drinking history 35 .…”

“…These drugs were selected because each has high addiction potential in clinical populations, they are ingested orally by mice [23][24][25][26] and oral ingestion of these drugs has been shown to be reinforcing. [27][28][29][30] Further, the use of each of these drugs has demonstrated potentiation of alcohol intake, [31][32][33][34] and the use of these drugs has been shown to be potentiated by an alcohol drinking history. 35 The DID model was selected to evaluate intake of these drugs as it was the drinking paradigm that was used in the selective breeding of these mice.…”