The Combination of Metyrapone and Oxazepam for the Treatment of Cocaine and Other Drug Addictions

Goeders, Nicholas E.; Guerin, Glenn F.; Schmoutz, Christopher D.

doi:10.1016/b978-0-12-420118-7.00011-1

Cited by 10 publications

(5 citation statements)

References 238 publications

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“…Although it is well recognized that the HPA axis and corticosteroids are involved in drug sensitivity and in the process of addiction, what is less clear is whether individuals at risk of developing addiction have a heightened or a blunted response of HPA to stressful stimuli, thus being less or more sensitive to relapse after stressful stimuli or being less or more successful at quitting drug abuse (Lovallo, 2006 ; Schumann, 2006 ; Koob and Kreek, 2007 ; Fox et al, 2009 ; Paris et al, 2010 ; McKee et al, 2011 ; Sinha, 2011 ; van Leeuwen et al, 2011 ; Evans et al, 2012 ; Vinson and Brennan, 2013 ; Goeders et al, 2014 ). On the other hand in pre-clinical studies while it was reported that locomotor response to stress, anxious phenotype and high corticosterone (CORT) levels were related to heightened drug self-administration, later studies demonstrated that these factors were not predictive of development of addiction-like behavior (see Piazza and Deroche-Gamonet, 2013 for a review).…”

Section: Vulnerability To Stressmentioning

confidence: 99%

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

Cadoni

2016

Front. Neurosci.

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Today it is well acknowledged that both nature and nurture play important roles in the genesis of psychopathologies, including drug addiction. Increasing evidence suggests that genetic factors contribute for at least 40–60% of the variation in liability to drug dependence. Human genetic studies suggest that multiple genes of small effect, rather than single genes, contribute to the genesis of behavioral psychopathologies. Therefore, the use of inbred rat strains might provide a valuable tool to identify differences, linked to genotype, important in liability to addiction and related disorders. In this regard, Lewis and Fischer 344 inbred rats have been proposed as a model of genetic vulnerability to drug addiction, given their innate differences in sensitivity to the reinforcing and rewarding effects of drugs of abuse, as well their different responsiveness to stressful stimuli. This review will provide evidence in support of this model for the study of the genetic influence on addiction vulnerability, with particular emphasis on differences in mesolimbic dopamine (DA) transmission, rewarding and emotional function. It will be highlighted that Lewis and Fischer 344 rats differ not only in several indices of DA transmission and adaptive changes following repeated drug exposure, but also in hypothalamic-pituitary-adrenal (HPA) axis responsiveness, influencing not only the ability of the individual to cope with stressful events, but also interfering with rewarding and motivational processes, given the influence of corticosteroids on dopamine neuron functionality. Further differences between the two strains, as impulsivity or anxiousness, might contribute to their different proneness to addiction, and likely these features might be linked to their different DA neurotransmission plasticity. Although differences in other neurotransmitter systems might deserve further investigation, results from the reviewed studies might open new vistas in understanding aberrant deviations in reward and motivational functions.

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Section: Vulnerability To Stressmentioning

confidence: 99%

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

Cadoni

2016

Front. Neurosci.

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“…Historically, stress has also been shown to be an important contributor to many components of drug and alcohol addiction (for review see Goeders et al , 2014; Lu et al , 2003; Sinha et al , 2011; Stewart, 2003). In the case of alcohol use disorders, research has demonstrated that there is a very complicated and often reciprocal relationship between stress and alcohol use (Brady and Sonne, 1999; Pohorecky, 1991; Sillaber and Henniger, 2004; Sinha, 2012; Spanagel et al , 2014).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of acute versus chronic stress on ethanol sensitivity: Evidence for interactions on both behavioral and neuroimmune outcomes

Doremus-Fitzwater

Paniccia

Gano

et al. 2018

Brain, Behavior, and Immunity

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Acute alcohol intoxication induces significant alterations in brain cytokines. Since stress challenges also profoundly impact central cytokine expression, these experiments examined the influence of acute and chronic stress on ethanol-induced brain cytokine responses. In Experiment 1, adult male rats were exposed to acute footshock. After a post-stress recovery interval of 0, 2, 4, or 24 h, rats were administered ethanol (4 g/kg; intragastric), with trunk blood and brains collected 3 h later. In non-stressed controls, acute ethanol increased expression of Il-6 and IκBα in the hippocampus. In contrast, rats exposed to footshock 24 h prior to ethanol demonstrated potentiation of hippocampal Il-6 and IκBα expression relative to ethanol-exposed non-stressed controls. Experiment 2 subsequently examined the effects of chronic stress on ethanol-related cytokine expression. Following a novel chronic escalating stress procedure, rats were intubated with ethanol. As expected, acute ethanol increased Il-6 expression in all structures examined, yet the Il-6 response was attenuated exclusively in the hippocampus in chronically stressed rats. Later experiments determined that neither acute nor chronic stress affected ethanol pharmacokinetics. When ethanol hypnosis was examined, however, rats exposed to chronic stress awoke at significantly lower blood ethanol levels compared to acutely stressed rats, despite similar durations of ethanol-induced sedation. These data indicate that chronic stress may increase sensitivity to ethanol hypnosis. Together, these experiments demonstrate an intriguing interaction between recent stress history and ethanol-induced increases in hippocampal Il-6, and may provide insight into novel pharmacotherapeutic targets for prevention and treatment of alcohol-related health outcomes based on stress susceptibility.

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“…For example, BZs have been reported to increase many of the abuse-related effects of opioids (Ator et al, 2005; Busto et al, 1996; Iguchi et al, 1993; Farre et al, 1998; Lintzeris et al, 2006; Preston et al, 1984; Spiga et al, 2001; Walker and Ettenberg, 2003), which is thought to contribute to the high incidence of their co-abuse (see Jones et al, 2012 for review). Conversely, BZs appear to reduce the abuse-related effects of psychostimulants (Augier et al, 2012; Barrett et al, 2005; Goeders et al, 2014; Lile et al, 2011; Marks et al, 2014; Weerts et al, 2005) commensurate with the seemingly low prevalence of their co-administration (but see Wolf et al, 2005). …”

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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The Combination of Metyrapone and Oxazepam for the Treatment of Cocaine and Other Drug Addictions

Cited by 10 publications

References 238 publications

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

Fischer 344 and Lewis Rat Strains as a Model of Genetic Vulnerability to Drug Addiction

Differential effects of acute versus chronic stress on ethanol sensitivity: Evidence for interactions on both behavioral and neuroimmune outcomes

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

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