# Disruption of Dopamine Homeostasis by Psychostimulants

**Authors:** Juan Torres, Colton Bredenkamp, Atzin Vazquez, Ernest T. Chivero

PMC · DOI: 10.1007/s12035-026-05769-0 · Molecular Neurobiology · 2026-03-05

## TL;DR

This paper reviews how drugs like cocaine and methamphetamine disrupt dopamine balance in the brain, leading to cognitive and emotional issues.

## Contribution

The paper provides a comprehensive overview of psychostimulant-induced dopamine system disruption and suggests future research directions for neuroprotective therapies.

## Key findings

- Psychostimulants disrupt dopamine synthesis, storage, release, and reuptake.
- Disruption leads to receptor desensitization, oxidative stress, and neuronal damage.
- Maintaining dopamine balance is crucial to prevent cognitive deficits and emotional dysregulation.

## Abstract

Dopamine is a catecholamine that acts as a modulatory neurotransmitter in the central nervous system. Although dopamine levels are kept within appropriate ranges through various mechanisms, they can be disrupted by multiple factors, including external psychostimulants such as cocaine and methamphetamine. Disruption contributes to cognitive deficits and emotional dysregulation that is associated with psychostimulant-use disorders (PSUD). These stimulants interfere with the dopamine system through various mechanisms that affect its synthesis, storage, release, reuptake, and degradation. Such changes have neurobiological effects, including receptor desensitization, oxidative stress, and neuronal damage, highlighting the importance of maintaining a balanced dopamine system. This review offers a comprehensive overview of how psychostimulants like cocaine and methamphetamine disrupt dopamine synthesis, storage, release, and reuptake, examines the neurobiological consequences of these disruptions, and proposes directions for future research on mechanisms and the development of novel neuroprotective therapies.

## Linked entities

- **Chemicals:** cocaine (PubChem CID 2826), methamphetamine (PubChem CID 1206), dopamine (PubChem CID 681)

## Full-text entities

- **Genes:** Slc18a2 (solute carrier family 18 (vesicular monoamine), member 2) [NCBI Gene 214084] {aka 1110037L13Rik, 9330105E13, Vmat2}, Pah (phenylalanine hydroxylase) [NCBI Gene 18478], Maob (monoamine oxidase B) [NCBI Gene 25750], Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 314322] {aka c-fos}, Aldh3a1 (aldehyde dehydrogenase family 3, subfamily A1) [NCBI Gene 11670] {aka Ahd-4, Ahd4, Aldh, Aldh3}, TH (tyrosine hydroxylase) [NCBI Gene 7054] {aka DYT14, DYT5b, TYH}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Maoa (monoamine oxidase A) [NCBI Gene 29253] {aka Mao}, Maob (monoamine oxidase B) [NCBI Gene 109731] {aka 6330414K01Rik, MAO-B}, Cav1 (caveolin 1, caveolae protein) [NCBI Gene 12389] {aka Cav, Cav-1}, TLR5 (toll like receptor 5) [NCBI Gene 7100] {aka MELIOS, SLE1, SLEB1, TIL3}, COMT (catechol-O-methyltransferase) [NCBI Gene 1312] {aka HEL-S-98n}, Maoa (monoamine oxidase A) [NCBI Gene 17161] {aka 1110061B18Rik}, Prkcd (protein kinase C, delta) [NCBI Gene 18753] {aka D14Ertd420e, PKC[d], PKCdelta, Pkcd}, Ppp2ca (protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform) [NCBI Gene 19052] {aka PP2A}, Slc18a2 (solute carrier family 18 member A2) [NCBI Gene 25549] {aka MNAT, VMAT-2, VMAT2}, Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Ephb2 (Eph receptor B2) [NCBI Gene 13844] {aka Cek5, Drt, ETECK, Erk, Hek5, Nuk}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, Ddc (dopa decarboxylase) [NCBI Gene 13195] {aka Aadc}, Fosb (FosB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 100360880] {aka fra-2}, SLC18A2 (solute carrier family 18 member A2) [NCBI Gene 6571] {aka PKDYS2, SVAT, SVMT, VAT2, VMAT2}, Fosb (Fos B proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14282], Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, Drd2 (dopamine receptor D2) [NCBI Gene 13489] {aka D2R, Drd-2}, MAOB (monoamine oxidase B) [NCBI Gene 4129], Akr1b1 (aldo-keto reductase family 1 member B) [NCBI Gene 11677] {aka ALR2, AR, Ahr-1, Ahr1, Akr1b3, Aldor1}, Drd1 (dopamine receptor D1) [NCBI Gene 13488] {aka C030036C15Rik, Drd-1, Drd1a, Gpcr15}, Prkcb (protein kinase C, beta) [NCBI Gene 18751] {aka PKC-B, PKC-Beta, Pkcb, Prkcb1, Prkcb2}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Slc6a3 (solute carrier family 6 (neurotransmitter transporter, dopamine), member 3) [NCBI Gene 13162] {aka DAT, Dat1}, Cacna1c (calcium channel, voltage-dependent, L type, alpha 1C subunit) [NCBI Gene 12288] {aka Cav1.2, Cchl1a1, D930026N18Rik, MBC, MELC-CC}, Akr1a1 (aldo-keto reductase family 1, member A1) [NCBI Gene 58810] {aka 2610201A18Rik, Akr1a4}
- **Diseases:** cravings (MESH:C564883), neurodegeneration (MESH:D019636), narcolepsy (MESH:D009290), PSUD (MESH:D000437), PD (MESH:D010300), paranoia (MESH:D010259), Addiction (MESH:D019966), irritability (MESH:D001523), sexually transmitted diseases (MESH:D012749), Neurotoxicity (MESH:D020258), morphine addiction (MESH:D009021), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), obesity (MESH:D009765), mood disorders (MESH:D019964), strokes (MESH:D020521), executive functioning (MESH:D003291), fatigue (MESH:D005221), diminished learning ability (MESH:D007859), Hyperthermia (MESH:D005334), opioid (MESH:D009293), neurological disorders (MESH:D009461), major depression (MESH:D003865), emotional dysregulation (MESH:D021081), cardiotoxicity (MESH:D066126), seizures (MESH:D012640), death (MESH:D003643), ADHD (MESH:D001289), psychosis (MESH:D011618), agitation (MESH:D011595), cocaine (MESH:D019970), lethargy (MESH:D053609), weight loss (MESH:D015431), depressed mood (MESH:D003866), Neuronal Damage (MESH:D009410), compulsive drug-seeking (MESH:D000081015), impulsive behavior (MESH:D010554), cardiac complications (MESH:D006331), necrosis (MESH:D009336), memory issues (MESH:D008569), overdose (MESH:D062787), dopaminergic (MESH:D009422), Cognitive and Emotional Deficits (MESH:D003072)
- **Chemicals:** Ibudilast (MESH:C038366), DA (MESH:C025953), HVA (MESH:D006719), SCH23390 (MESH:C534628), Bupropion (MESH:D016642), 3,4-dihydroxyphenylacetic acid (MESH:D015102), 3-methoxytyramine (MESH:C001746), Tyrosine (MESH:D014443), H89 (MESH:C063509), AMPT (MESH:D019805), amphetamine (MESH:D000661), glutamate (MESH:D018698), GABA (MESH:D005680), N-methyl-D-aspartate (MESH:D016202), hydroxyl radicals (MESH:D017665), risperidone (MESH:D018967), melatonin (MESH:D008550), Disulfiram (MESH:D004221), 5-HIAA (MESH:D006897), Methamphetamine (MESH:D008694), H2O2 (MESH:D006861), DAPAC (-), superoxide anions (MESH:D013481), 7,8-dihydroxyflavone (MESH:C485383), Na+ (MESH:D012964), crack cocaine (MESH:D016578), ceftriaxone (MESH:D002443), Cocaine (MESH:D003042), amino acid (MESH:D000596), catecholamine (MESH:D002395), nicotine (MESH:D009538), DOPA (MESH:D004295), clorgyline (MESH:D003010), Naltrexone (MESH:D009271), phenylalanine (MESH:D010649), Cl- (MESH:D002713), deprenyl (MESH:D012642), rasagiline (MESH:C031967), Modafinil (MESH:D000077408), eticlopride (MESH:C045989), SKF38393 (MESH:D015647), rottlerin (MESH:C085746), 125I (MESH:C000614960), 11C (MESH:C000615233), pargyline (MESH:D010293), lipids (MESH:D008055), amphetamines (MESH:D000662), Topiramate (MESH:D000077236), alcohol (MESH:D000438), morphine (MESH:D009020), Dopamine (MESH:D004298), cannabinoids (MESH:D002186), ROS (MESH:D017382), RTI-121 (MESH:C079213), calcium (MESH:D002118), Entolimod (MESH:C528306), glucose (MESH:D005947), 3,4-dihydroxyphenylacetaldehyde (MESH:C007430)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs4680, Met/Met, Val/Val

## Full text

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## Figures

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## References

9 references — full list in the complete paper: https://tomesphere.com/paper/PMC12963094/full.md

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Source: https://tomesphere.com/paper/PMC12963094