Sources of variation in the design of preclinical studies assessing the effects of amphetamine-type stimulants in pregnancy and lactation

McDonnell‐Dowling, Kate; Kelly, John

doi:10.1016/j.bbr.2014.11.021

Cited by 13 publications

(19 citation statements)

References 103 publications

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“…Furthermore, the split litter design provides some control over the metagenome and microbiome (Stappenbeck and Virgin 2016). While McDonnell-Dowling and Kelly (2015) suggest the possibility of inadvertent MA exposure to the dam or control pups via MA-treated pups’ excrement, there are no data to support this speculation.…”

Section: Methodsmentioning

confidence: 99%

Effects of Neonatal Methamphetamine and Stress on Brain Monoamines and Corticosterone in Preweanling Rats

2016

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Neonatal exposure to methamphetamine (MA) and developmental chronic stress significantly alter neurodevelopmental profiles that show a variety of long-term physiological and behavioral effects. In the current experiment, Sprague-Dawley rats were exposed to one of two housing conditions along with MA. Rats were given 0 (saline), 5, or 7.5 mg/kg MA, four times per day from postnatal day (P)11 to 15 or P11 to 20. Half of the litters were reared in cages with standard bedding and half with no bedding. Separate litters were assessed at P15 or P20 for organ weights (adrenals, spleen, thymus); corticosterone; and monoamine assessments (dopamine, serotonin, norepinephrine) and their metabolites within the neostriatum, hippocampus, and prefrontal cortex. Findings show neonatal MA altered mono-amines, corticosterone, and organ characteristics alone, and as a function of developmental age and stress compared with controls. These alterations may in part be responsible for MA and early life stress-induced long-term learning and memory deficits.

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Section: Methodsmentioning

confidence: 99%

Effects of Neonatal Methamphetamine and Stress on Brain Monoamines and Corticosterone in Preweanling Rats

2016

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“…We previously classified these MA doses into neurotoxic, toxic and pharmacological [17] and Table 1 classifies the MA doses used from these studies accordingly. Although some studies have looked at lower MA doses (pharmacological and toxic), most of the doses employed to date have fallen into the neurotoxic class range (i.e.…”

Section: How To Measure Oxidative Stress?mentioning

confidence: 99%

“…The range of doses used in MA oxidative stress preclinical studies (Adapted from McDonnell-Dowling and Kelly [17]. …”

Section: How To Measure Oxidative Stress?mentioning

confidence: 99%

“…The pharmacological doses (0.25-2 mg/kg) and low toxic doses (2-3 mg/kg) of MA (Table 1 ) are the doses that equate to those most commonly abused in the clinical scenario [17]. Therefore it is pertinent that such doses have shown to yield the greatest results for oxidative stress as it allows for comparison of these preclinical studies to what is happening in the human situation.…”

Section: How To Measure Oxidative Stress?mentioning

confidence: 99%

“…A comparison of these routes would highlight if there are any differences and if the terminal time point needs to be altered based on the route of administration used. Returning again to the clinical situation then we know that oral use or use through inhalation is how MA is most commonly abused in humans [17] but this has been overlooked in preclinical studies to date and so this should also be included in future research.…”

Section: How To Measure Oxidative Stress?mentioning

confidence: 99%

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The Role of Oxidative Stress in Methamphetamine-induced Toxicity and Sources of Variation in the Design of Animal Studies

McDonnell‐Dowling

Kelly²

2017

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BackgroundThe prevalence of methamphetamine (MA) use has increased in recent years. In order to assess how this drug produces its effects, both clinical and preclinical studies have recently begun to focus on oxidative stress as an important biochemical mechanism in mediating these effects.ObjectiveThe purpose of this review is to illustrate the variation in the design of preclinical studies investigating MA exposure on oxidative stress parameters in animal models.MethodThe experimental variables investigated and summarised include MA drug treatment, measurements of oxidative stress and antioxidant treatments that ameliorate the harmful effects of MA.ResultsThese preclinical studies differ greatly in their experimental design with respect to the dose of MA (ranging between 0.25 and 20 mg/kg), the dosing regime (acute, binge or chronic), the time of measurement of oxidative stress (0.5 h to 2 wks after last MA administration), the antioxidant system targeted and finally the use of antioxidants including the route of administration (i.p. or p.o.), the frequency of exposure and the time of exposure (preventative or therapeutic).ConclusionThe findings in this paper suggest that there is a large diversity among these studies and so the interpretation of these results is challenging. For this reason, the development of guidelines and how best to assess oxidative stress in animal models may be beneficial. The use of these simple recommendations mean that results will be more comparable between laboratories and that future results generated will give us a greater understanding of the contribution of this important biochemical mechanism and its implications for the clinical scenario.

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Daily, limited access to methamphetamine self‐administration during pregnancy leads to increased methamphetamine sensitivity in adult offspring

Pareek

Platt

Rüedi‐Bettschen

2022

Developmental Psychobiology

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Methamphetamine use by women, even throughout pregnancy, is common. But there is limited knowledge about the effects in prenatally methamphetamine-exposed children. This study investigated how prenatal methamphetamine exposure in rats, via maternal i.v. self-administration, affected the sensitivity of adult offspring to methamphetamine in comparison with controls. The offspring were generated from dams either self-administering methamphetamine daily under limited-access conditions prior to and throughout pregnancy, or their respective saline-yoked control dams. Spontaneous and methamphetamine-induced locomotor activity was assessed in male and female offspring of both exposure groups after a range of methamphetamine doses. In a separate group of offspring, acquisition of i.v. methamphetamine self-administration, responding under fixed and progressive ratio schedules of methamphetamine reinforcement, and reinstatement of extinguished drug-seeking behavior were assessed. Methamphetamine dose-dependently increased locomotor activity in both exposure groups. However, methamphetamine-exposed males showed significantly enhanced locomotor activity compared with controls at 1 mg/kg, and methamphetamine-exposed females showed significantly enhanced locomotor activity compared with controls at 3.2 mg/kg. Methamphetamine-exposed offspring of both sexes acquired methamphetamine self-administration faster and showed overall higher levels of methamphetamine-induced reinstatement compared with controls.Taken together, these results indicate that prenatal methamphetamine exposure to relatively low levels alters methamphetamine sensitivity in male and female adult offspring.

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Sources of variation in the design of preclinical studies assessing the effects of amphetamine-type stimulants in pregnancy and lactation

Cited by 13 publications

References 103 publications

Effects of Neonatal Methamphetamine and Stress on Brain Monoamines and Corticosterone in Preweanling Rats

Effects of Neonatal Methamphetamine and Stress on Brain Monoamines and Corticosterone in Preweanling Rats

The Role of Oxidative Stress in Methamphetamine-induced Toxicity and Sources of Variation in the Design of Animal Studies

Daily, limited access to methamphetamine self‐administration during pregnancy leads to increased methamphetamine sensitivity in adult offspring

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