Role of the dopamine uptake carrier in the neurochemical response to methamphetamine: Effects of amfonelic acid

doi:10.1016/0014-2999(85)90541-2

European Journal of Pharmacology

Volume 109, Issue 1, 12 February 1985, Pages 73-80

https://doi.org/10.1016/0014-2999(85)90541-2 Get rights and content

Abstract

Repeated administration of large doses of methamphetamine depresses both neostriatal tyrosine hydroxylase and tryptophan hydroxylase activity. Neostriatal concentrations of dopamine, serotonin and their acidic metabolites are similarly reduced by methamphetamine. Coadministration of the dopamine uptake inhibitor, amfonelic acid, selectively prevented the methamphetamine-induced decrease in tyrosine hydroxylase activity while not altering the depression of tryptophan hydroxylase activity. In vitro, amfonelic acid blocked methamphetamine-induced [³H]dopamine release from neostriatal slices but had no effect on [³H]serotonin release. In experiments conducted with [³H]amphetamine and amfonelic acid, no evidence was found for carrier-mediated transport of amphetamine. The results demonstrate a role for the dopamine uptake carrier in the neurochemical effects of high doses of methamphetamine. Furthermore, the ability of amfonelic acid to antagonize the neurochemical effects of methamphetamine appears to be due to an inhibition of carrier-mediated dopamine efflux rather than carrier-mediated uptake of methamphetamine.

References (24)

C. Bakhit et al.
Methamphetamine-induced depression of tryptophan hydroxylase: recovery following acute treatment
European J. Pharmacol.
(1981)
C. Bakhit et al.
Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain
Neuropharmacology
(1981)
M.K. Buening et al.
Influence of methamphetamine and neuroleptic drugs on tyrosine hydroxylase activity
European J. Pharmacol.
(1974)
H.C. Fibiger et al.
Effect of acute and chronic methamphetamine treatment on tyrosine hydroxylase activity in brain and adrenal medulla
European J. Pharmacol.
(1971)
C.T. Giambalvo et al.
Effect of p-chloroamphetamine and 5,7-dihydroxytryptamine on rotation and dopamine turnover
Brain Res.
(1978)
R.E. Heikkila et al.
Pharmacological studies with several analogs of mazindol: correlation between effects on dopamine uptake and various in vivo responses
European J. Pharmacol.
(1981)
A.J. Hotchkiss et al.
Blockade of methamphetamine-induced depression of tyrosine hydroxylase by GABA-transaminase inhibitors
European J. Pharmacol.
(1980)
N.Y. Liang et al.
Comparison of the release of [³H]dopamine from isolated corpus striatum by amphetamine, fenfluramine and unlabeled dopamine
Biochem. Pharmacol.
(1982)
N.Y. Liang et al.
Evidence for carriermediated efflux of dopamine from corpus striatum
Biochem. Pharmacol.
(1982)
D.T. Masuoka et al.
[³H]Dopamine release from neostriatal synaptosomes of reserpinized rats
Biochem. Pharmacol.
(1982)

T. Nagatsu et al.

A rapid and simple radioassay for tyrosine hydroxylase

Anal. Biochem.

(1964)

L.R. Steranka

Long-term decreases in neostriatal dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid after a single injection of amphetamine in iprindole-treated rats: time course and time-dependent interactions with amfonelic acid

Brain Res.

(1982)

Cited by (109)

Autophagy as a gateway for the effects of methamphetamine: From neurotransmitter release and synaptic plasticity to psychiatric and neurodegenerative disorders
2021, Progress in Neurobiology
As a major eukaryotic cell clearing machinery, autophagy grants cell proteostasis, which is key for neurotransmitter release, synaptic plasticity, and neuronal survival. In line with this, besides neuropathological events, autophagy dysfunctions are bound to synaptic alterations that occur in mental disorders, and early on, in neurodegenerative diseases. This is also the case of methamphetamine (METH) abuse, which leads to psychiatric disturbances and neurotoxicity. While consistently altering the autophagy machinery, METH produces behavioral and neurotoxic effects through molecular and biochemical events that can be recapitulated by autophagy blockade. These consist of altered physiological dopamine (DA) release, abnormal stimulation of DA and glutamate receptors, as well as oxidative, excitotoxic, and neuroinflammatory events. Recent molecular insights suggest that METH early impairs the autophagy machinery, though its functional significance remains to be investigated. Here we discuss evidence suggesting that alterations of DA transmission and autophagy are intermingled within a chain of events underlying behavioral alterations and neurodegenerative phenomena produced by METH. Understanding how METH alters the autophagy machinery is expected to provide novel insights into the neurobiology of METH addiction sharing some features with psychiatric disorders and parkinsonism.
Abuse potential and toxicity of the synthetic cathinones (i.e., “Bath salts”)
2020, Neuroscience and Biobehavioral Reviews
The synthetic cathinones are derived from the naturally occurring drug cathinone found in the khat plant (Catha edulis) and have chemical structures and neurochemical consequences similar to other psychostimulants. This class of new psychoactive substances (NPS) also has potential for use and abuse coupled with a range of possible adverse effects including neurotoxicity and lethality. This review provides a general background of the synthetic cathinones in terms of the motivation for and patterns and demographics of their use as well as the behavioral and physiological effects that led to their spread as abused substances and consequent regulatory control. This background is followed by a review focusing on their rewarding and aversive effects as assessed in various pre-clinical animal models and the contribution of these effects to their self-administration (implicating their use and abuse potential). The review closes with an overview of the consequences of synthetic cathinone use and abuse in terms of their potential to produce neurotoxicity and lethality. These characterizations are discussed in the context of other classical psychostimulants.
Drug-induced neurotoxicity in addiction medicine: From prevention to harm reduction
2016, Progress in Brain Research
Citation Excerpt :
As mentioned above, dopamine plays a pivotal role in mediating methamphetamine-induced neurotoxicity by causing production of dopamine-related reactive oxygen species (ROS) and oxidative stress. Agents decreasing brain dopamine levels such as tyrosine hydroxylase inhibitor and α-methyl-p-tyrosine have indeed shown to exert protective effects against the neurotoxicity induced by methamphetamine in striatal dopaminergic axons (Axt et al., 1990; Gibb and Kogan, 1979; Hotchkiss and Gibb, 1980; Schmidt and Gibb, 1985; Thomas et al., 2008). Pramipexole, a dopamine D2/D3 receptor agonist, may cause neuroprotection against methamphetamine-induced toxicity by reducing dopamine turnover by stimulation of presynaptic dopamine receptors or by increasing antioxidant and trophic properties of the brain (Hall et al., 1996).
Neurotoxicity is considered as a major cause of neurodegenerative disorders. Most drugs of abuse have nonnegligible neurotoxic effects many of which are primarily mediated by several dopaminergic and glutamatergic neurotransmitter systems. Although many researchers have investigated the medical and cognitive consequences of drug abuse, the neurotoxicity induced by these drugs still requires comprehensive attention. The science of neurotoxicity promises to improve preventive and therapeutic strategies for brain disorders such as Alzheimer disease and Parkinson's disease. However, its clinical applications for addiction medicine remain to be defined adequately. This chapter reviews the most commonly discussed mechanisms underlying neurotoxicity induced by common drugs of abuse including amphetamines, cocaine, opiates, and alcohol. In addition, the known factors that trigger and/or predispose to drug-induced neurotoxicity are discussed. These factors include drug-related, individual-related, and environmental insults. Moreover, we introduce some of the potential pharmacological antineurotoxic interventions deduced from experimental animal studies. These interventions involve various targets such as dopaminergic system, mitochondria, cell death signaling, and NMDA receptors, among others. We conclude the chapter with a discussion of addicted patients who might benefit from such interventions.
Novel multifunctional pharmacology of lobinaline, the major alkaloid from Lobelia cardinalis
2016, Fitoterapia
Citation Excerpt :
The latter study suggests an intact neurological system is required to examine modulation of DAT activity by nicAchR agonists. As described above, lobinaline exerts pleiotropic pharmacological effects relevant to the prevention and/or reduction of DAergic neurotoxicity seen in PD and psychostimulant abuse, including nicAchR activation and DAT inhibitory modulation [6–10,13,26–31]. Since multiple lines of evidence indicate excessive free radical production contributes to DAergic neurotoxicity seen in the aforementioned pathologies, lobinaline was assessed for its capacity to scavenge free radicals [28,30,33,42–44].
In screening a library of plant extracts from ~ 1000 species native to the Southeastern United States, Lobelia cardinalis was identified as containing nicotinic acetylcholine receptor (nicAchR) binding activity which was relatively non-selective for the α₄β₂- and α₇-nicAchR subtypes. This nicAchR binding profile is atypical for plant-derived nicAchR ligands, the majority of which are highly selective for α₄β₂-nicAchRs. Its potential therapeutic relevance is noteworthy since agonism of α₄β₂- and α₇-nicAchRs is associated with anti-inflammatory and neuroprotective properties. Bioassay-guided fractionation of L. cardinalis extracts led to the identification of lobinaline, a complex binitrogenous alkaloid, as the main source of the unique nicAchR binding profile. Purified lobinaline was a potent free radical scavenger, displayed similar binding affinity at α₄β₂- and α₇-nicAchRs, exhibited agonist activity at nicAchRs in SH-SY5Y cells, and inhibited [³H]-dopamine (DA) uptake in rat striatal synaptosomes. Lobinaline significantly increased fractional [³H] release from superfused rat striatal slices preloaded with [³H]-DA, an effect that was inhibited by the non-selective nicAchR antagonist mecamylamine. In vivo electrochemical studies in urethane-anesthetized rats demonstrated that lobinaline locally applied in the striatum significantly prolonged clearance of exogenous DA by the dopamine transporter (DAT). In contrast, lobeline, the most thoroughly investigated Lobelia alkaloid, is an α₄β₂-nicAchR antagonist, a poor free radical scavenger, and is a less potent DAT inhibitor. These previously unreported multifunctional effects of lobinaline make it of interest as a lead to develop therapeutics for neuropathological disorders that involve free radical generation, cholinergic, and dopaminergic neurotransmission. These include neurodegenerative conditions, such as Parkinson's disease, and drug abuse.
Mephedrone: An Overview of Its Neurotoxic Potential
2016, Neuropathology of Drug Addictions and Substance Misuse
Mephedrone is a synthetic psychoactive drug of abuse that has gained notoriety as one of the constituents of so-called “bath salts.” Mephedrone is very similar in chemical structure to methamphetamine, another psychotropic drug of abuse that is well-known to cause neurotoxicity in humans. Key facets of methamphetamine action that are thought to be critical for its ability to damage the brain include stimulation of nonvesicular release of dopamine and inhibition of its reuptake by the dopamine transporter, inhibition of dopamine metabolism, and significant increases in core body temperature. Early pharmacological studies established that mephedrone shares all of these actions with methamphetamine, leading to the prediction that it would cause damage to at least dopamine nerve endings. Research reviewed in this chapter shows that high-dose mephedrone, against expectations, does not lead to persistent neurotoxicity. Mephedrone (and other related “bath salts” components) may therefore offer insight into those unique structural features that render it nonneurotoxic compared with methamphetamine.
Mephedrone: An Overview of Its Neurotoxic Potential
2016, Neuropathology of Drug Addictions and Substance Misuse Volume 2: Stimulants, Club and Dissociative Drugs, Hallucinogens, Steroids, Inhalants and International Aspects
Mephedrone is a synthetic psychoactive drug of abuse that has gained notoriety as one of the constituents of so-called “bath salts.” Mephedrone is very similar in chemical structure to methamphetamine, another psychotropic drug of abuse that is well-known to cause neurotoxicity in humans. Key facets of methamphetamine action that are thought to be critical for its ability to damage the brain include stimulation of nonvesicular release of dopamine and inhibition of its reuptake by the dopamine transporter, inhibition of dopamine metabolism, and significant increases in core body temperature. Early pharmacological studies established that mephedrone shares all of these actions with methamphetamine, leading to the prediction that it would cause damage to at least dopamine nerve endings. Research reviewed in this chapter shows that high-dose mephedrone, against expectations, does not lead to persistent neurotoxicity. Mephedrone (and other related “bath salts” components) may therefore offer insight into those unique structural features that render it nonneurotoxic compared with methamphetamine.

View all citing articles on Scopus

View full text

Role of the dopamine uptake carrier in the neurochemical response to methamphetamine: Effects of amfonelic acid

Abstract

European J. Pharmacol.

Neuropharmacology

European J. Pharmacol.

European J. Pharmacol.

Brain Res.

European J. Pharmacol.

European J. Pharmacol.

Biochem. Pharmacol.

Biochem. Pharmacol.

Biochem. Pharmacol.

Anal. Biochem.

Brain Res.