The acute effects of multiple doses of methamphetamine on locomotor activity and anxiety-like behavior in adolescent and adult mice

Ortman, Hayley A.; Newby, Mikayla L.; Acevedo, Jonathan; Siegel, Jessica A.

doi:10.1016/j.bbr.2021.113186

Cited by 13 publications

(5 citation statements)

References 56 publications

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“…In this study, we also observed that 1 mg/kg of 25D-NBOMe significantly increased the CPP. This result suggests that 25D-NBOMe has the same rewarding effect, as structurally similar drugs, such as 25B-NBOMe and 25N-NBOMe. , Based on previous studies, − acute and chronic METH treatments could increase locomotor activity. In addition, 3,4-methylenedioxymethamphetamine (MDMA), as a 5-HT 2A receptor agonist and hallucinogen, increased locomotor activity.…”

Section: Discussionmentioning

confidence: 60%

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System

Lee

Jang

Hwang

et al. 2023

ACS Chem. Neurosci.

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2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)_ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT 2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT (p-DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.

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Section: Discussionmentioning

confidence: 60%

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System

Lee

Jang

Hwang

et al. 2023

ACS Chem. Neurosci.

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“…A similar pattern was observed when combined with fentanyl, whereby low doses of METH exacerbated opioid-induced respiratory depression (OIRD), but a high dose reversed OIRD (Elder et al, 2023a). These bidirectional effects of METH on respiratory parameters should be of particular relevance to toxicity caused by nonmedical use because they are induced by doses that would be expected to produce plasma levels similar to those achieved in humans (Mendelson et al, 2006;Ortman et al, 2021;Rauhut and Bialecki, 2011). Both the respiratory stimulant and depressant effects of METH have potential consequences for treating polydrug toxicity and OIRD in that pro-depressant effects may complicate resuscitation following opioid overdose, and stimulatory effects may be exploited for the development of opioid receptor-independent analeptics.…”

Section: Introductionmentioning

confidence: 62%

Enantiomeric and Monoaminergic Contributions to Methamphetamine's Bidirectional Effects on Fentanyl-Depressed Respiration in Mice

Elder,

Walentiny,

Beardsley

2023

Preprint

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Rationale: Fentanyl remains the primary cause of fatal overdoses, and its co-use with methamphetamine (METH) is a growing concern. The optical isomers of METH, dextromethamphetamine (d-METH) and levomethamphetamine (l-METH), differ substantially in dose expression and thus may differentially contribute to the racemate’s bidirectional effects. Furthermore, it is unknown which of METH’s monoamine (MA) receptor mechanisms mediate these respiratory effects. Thus, systematic evaluation of monoamine receptor selective agents may identify treatment targets for OIRD. Methods: The two optical isomers of METH, d-METH and l-METH, were tested in adult male mice to determine their effects on basal and fentanyl-depressed minute volume (MVb; i.e., respiratory frequency x tidal volum) using whole-body plethysmography. Next, six selective agonists at MA receptors involved in METH’s activity [phenylephrine (PNE; α1), clonidine (CLON; α2), SKF-82958 (SKF; D1), quinpirole (QPR; D2), 8-OH-DPAT (8-OH; 5HT1A), and DOI (5HT2)] were singly tested on basal MVb, and then in combination with fentanyl. Results: d-METH elevated MVb and l-METH decreased MVb. Under fentanyl-depressed conditions, the bidirectional effects of racemic METH were recreated by d-METH while l-METH significantly exacerbated OIRD at 1.0 and 3.0 mg/kg. MVb was dose-dependently increased by PNE and SKF and decreased by CLON and QPR. Neither 8-OH nor DOI altered basal MVb. Under fentanyl-depressed conditions, SKF transiently elevated MVb, while PNE more persistently increased it, while DOI transiently increased MVb, and 8-OH decreased MVb. Conclusions: d-METH and l-METH differentially contribute to the bidirectional respiratory modulation observed with the racemate and selective activation of MA receptors altered basal respiration and OIRD.

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“…These observations suggest reduced anxiety-like behavior and increased exploratory tendencies in the tested animals. The travelled distance is an expression of locomotor activity in rodents [ 47 ], while time spent in open arms, frequency of defecation, and frequency of rearing are expressions of the level of depression in rodents [ 48 ]. Based on the EPM, we can evaluate the level of anxiety in rodents, which increased with decreasing time spent in the open arms of the maze by rodents and with lower number of passes through the center of the maze [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

The First In Vivo Study Shows That Gyrophoric Acid Changes Behavior of Healthy Laboratory Rats

Simko,

Leskanicova,

Suvakova-Nunhart

et al. 2024

IJMS

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Gyrophoric acid (GA), a lichen secondary metabolite, has attracted more attention during the last years because of its potential biological effects. Until now, its effect in vivo has not yet been demonstrated. The aim of our study was to evaluate the basic physicochemical and pharmacokinetic properties of GA, which are directly associated with its biological activities. The stability of the GA in various pH was assessed by conducting repeated UV-VIS spectral measurements. Microsomal stability in rat liver microsomes was performed using Ultra-Performance LC/MS. Binding to human serum albumin (HSA) was assessed using synchronous fluorescence spectra, and molecular docking analysis was used to reveal the binding site of GA to HSA. In the in vivo experiment, 24 Sprague-Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided as follows. The first group (n = 6) included healthy males as control intact rats (♂INT), and the second group (n = 6) included healthy females as controls (♀INT). Groups three and four (♂GA/n = 6 and ♀GA/n = 6) consisted of animals with daily administered GA (10 mg/kg body weight) in an ethanol-water solution per os for a one-month period. We found that GA remained stable under various pH and temperature conditions. It bonded to human serum albumin with the binding constant 1.788 × 106 dm3mol−1 to reach the target tissue via this mechanism. In vivo, GA did not influence body mass gain, food, or fluid intake during the experiment. No liver toxicity was observed. However, GA increased the rearing frequency in behavioral tests (p < 0.01) and center crossings in the elevated plus-maze (p < 0.01 and p < 0.001, respectively). In addition, the time spent in the open arm was prolonged (p < 0.01 and p < 0.001, respectively). Notably, GA was able to pass through the blood–brain barrier, indicating its ability to permeate into the brain and to stimulate neurogenesis in the hilus and subgranular zone of the hippocampus. These observations highlight the potential role of GA in influencing brain function and neurogenesis.

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The acute effects of multiple doses of methamphetamine on locomotor activity and anxiety-like behavior in adolescent and adult mice

Cited by 13 publications

References 56 publications

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System

Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System

Enantiomeric and Monoaminergic Contributions to Methamphetamine's Bidirectional Effects on Fentanyl-Depressed Respiration in Mice

The First In Vivo Study Shows That Gyrophoric Acid Changes Behavior of Healthy Laboratory Rats

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