Anxiogenic Effect of Low-dose Methamphetamine in the Test of Elevated Plus-maze

Pometlová, Marie; Nohejlová-Deykun, K.; Šlamberová, Romana

doi:10.14712/23362936.2015.20

Cited by 20 publications

(7 citation statements)

References 19 publications

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“…METH increased anxiety due to its stimulant effects, as verified in the present study, consistent with results from human and rodent studies (Pometlova et al, 2012; Salo et al, 2011). During the chronic METH protocol, anxiety was assessed within one hour after administration of the drug, when circulating levels of METH would still be significantly elevated (Riviere et al, 1999).…”

Section: Discussionsupporting

confidence: 93%

A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence

2013

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Methamphetamine (METH) is an addictive stimulant drug. In addition to drug craving and lethargy, METH withdrawal is associated with stress-triggered anxiety. However, the cellular basis for this stress-triggered anxiety is not understood. The present results suggest that during METH withdrawal (24 h) following chronic exposure (3 mg/kg, i.p. for 3-5 weeks) of adult, male mice, the effect of one neurosteroid released by stress, 3α,5α-THP (3α-OH-5α-pregnan-20-one), and its 3α,5β isomer reverse to trigger anxiety assessed by the acoustic startle response (ASR), in contrast to their usual anti-anxiety effects. This novel effect of 3α,5β-THP was due to increased (3-fold) hippocampal expression of α4βδ GABAA receptors (GABARs) during METH withdrawal (24 h – 4 wk) because anxiogenic effects of 3α,5β-THP were not seen in α4−/− mice. 3α,5β-THP reduces current at these receptors when it is hyperpolarizing, as observed during METH withdrawal. As a result, 3α,5β-THP (30 nM) increased neuronal excitability, assessed with current clamp and cell-attached recordings in CA1 hippocampus, one CNS site which regulates anxiety. α4βδ GABARs were first increased 1 h after METH exposure and recovered 6 wk after METH withdrawal. Similar increases in α4βδ GABARs and anxiogenic effects of 3α,5β-THP were noted in rats during METH withdrawal (24 h). In contrast, the ASR was increased by chronic METH treatment in the absence of 3α,5β-THP administration due to its stimulant effect. Although α4βδ GABARs were increased by chronic METH treatment, the GABAergic current recorded from hippocampal neurons at this time was a depolarizing, shunting inhibition, which was potentiated by 3α,5β-THP. This steroid reduced neuronal excitability and anxiety during chronic METH treatment, consistent with its typical effect. Flumazenil (10 mg/kg, i.p., 3x) reduced α4βδ expression and prevented the anxiogenic effect of 3α,5β-THP after METH withdrawal. Our findings suggest a novel mechanism underlying stress-triggered anxiety after METH withdrawal mediated by α4βδ GABARs.

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Section: Discussionsupporting

confidence: 93%

A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence

2013

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“…The same method was used as in our previous study [46], which was a modified protocol of Fernández Espejo [16]. All animals were habituated to the laboratory environment and the experimenter during the 3 days prior to the experiment [22].…”

Section: Elevated Plus Maze (Epm)mentioning

confidence: 99%

Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

Šlamberová

Pometlová

Macúchová

et al. 2015

Behavioural Brain Research

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“…The same method was used as in our previous study (Pometlová et al, 2012), which was a modified protocol of Fernández Espejo (1997). All animals were habituated to the laboratory environment and the experimenter during the 3 days prior to the experiment (Geyer and Swerdlow, 2007).…”

Section: Elevated Plus-maze (Epm)mentioning

confidence: 99%

Can Anxiety Tested in the Elevated Plus-maze Be Related to Nociception Sensitivity in Adult Male Rats?

Pometlová¹,

Yamamotová²,

Nohejlová³

et al. 2016

Prague Med. Rep.

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Methamphetamine (MA) is one of the most addictive psychostimulant drugs with a high potential for abuse. Our previous studies demonstrated that MA administered to pregnant rats increases pain sensitivity and anxiety in their adult offspring and makes them more sensitive to acute administration of the same drug in adulthood. Because individuals can differ considerably in terms of behaviour and physiology, such as rats that do not belong in some characteristics (e.g. anxiety) to average, can be described as low-responders or high-responders, are then more or less sensitive to pain. Therefore, prenatally MA-exposed adult male rats treated in adulthood with a single dose of MA (1 mg/ml/kg) or saline (1 ml/kg) were tested in the present study. We examined the effect of acute MA treatment on: (1) the anxiety in the Elevated plus-maze (EPM) test and memory in EPM re-test; (2) nociception sensitivity in the Plantar test; (3) the correlation between the anxiety, memory and the nociception. Our results demonstrate that: (1) MA has an anxiogenic effect on animals prenatally exposed to the same drug in the EPM; (2) all the differences induced by acute MA treatment disappeared within the time of 48 hours; (3) there was no effect of MA on nociception per se, but MA induced higher anxiety in individuals less sensitive to pain than in animals more sensitive to pain. In conclusion, the present study demonstrates unique data showing association between anxiety and nociceptive sensitivity of prenatally MA-exposed rats that is induced by acute drug administration.

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Anxiogenic Effect of Low-dose Methamphetamine in the Test of Elevated Plus-maze

Cited by 20 publications

References 19 publications

A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence

A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence

Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

Can Anxiety Tested in the Elevated Plus-maze Be Related to Nociception Sensitivity in Adult Male Rats?

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