Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment

Kohno, Milky; Dennis, Laura; McCready, Holly; Hoffman, William F.

doi:10.1038/s41380-021-01180-4

Cited by 19 publications

(15 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The neurotransmitter dopamine plays roles in the basic modulation of the retina and the development of addiction [ 18 , 29 ]. In studies conducted on rodents, it was shown that psychostimulant substances such as amphetamine/methamphetamine increase extracellular dopamine release in acute intake [ 30 , 31 ]. However, in chronic, long-term exposure, they experience dopamine depletion at the striatal level [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

OCT Findings in Patients with Methamphetamine Use Disorder

Kaya

Kaya²

2023

JPM

View full text Add to dashboard Cite

Purpose: In the present study, the purpose was to examine the results of optical coherence tomography (OCT) measurements in patients diagnosed with methamphetamine use disorder (MUD) by comparing them with healthy controls. Materials and Methods: A total of 114 eyes were evaluated in this study (27 patients and 30 control group participants). After detailed biomicroscopic examinations of all participants by the same ophthalmologist, both eyes were evaluated by OCT. The retinal nerve fiber layer thickness (RNFL) and macular thickness were calculated from OCT. Results: No statistically significant differences were detected between the demographic data of the patient and control groups (p > 0.05). When OCT findings were evaluated, macular thickness and volume were not different between the groups (p > 0.05). With respect to RNFL, the left eye superior, inferior, temporal, and nasal quadrants, as well as the left eye’s total measurements were found to be thicker than those of controls (p < 0.05). In both eyes, the left eye nasal quadrant and APIS total score were negatively correlated, the total RNLF measurement of the right eye and APIS motivation subscale score were negatively correlated, central macular thickness and the APIS motivation subscale score were positively correlated, and the APIS substance use characteristics subscale score and left eye temporal quadrant RNLF measurement were positively correlated. Conclusion: Our study is the first to evaluate addiction severity and OCT findings in MUD. However, this study needs to be supported by further studies so that OCT findings, which can be used as an effective method for demonstrating possible neurodegeneration in methamphetamine use disorder, gain importance.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In post-mortem analyses, it is noteworthy that striatal dopamine levels were low in MUD patients. Both low dopamine levels and increased dopamine receptor sensitivity were reported [ 31 , 33 ]. With this mechanism in mind, it is thought that the RNLF layer may be increased in patients with MUD.…”

Section: Discussionmentioning

confidence: 99%

OCT Findings in Patients with Methamphetamine Use Disorder

Kaya

Kaya²

2023

JPM

View full text Add to dashboard Cite

show abstract

“…Konsument. Obwohl Amphetamin und Methamphetamin sehr ähnliche subjektive Wirkungen haben, wird angenommen, dass Methamphetamin aufgrund seiner stärkeren Wirkung auf das Dopaminsystem ein höheres Abhängigkeitspotenzial besitzt [16].…”

Section: Merkeunclassified

“…Die N-Methylgruppe des Methamphetamins führt zu einer höheren Fettlöslichkeit als Amphetamin und erleichtert somit den Transport der Substanz durch die Blut-Hirn-Schranke. Zusammen mit den stärkeren Ef-fekten auf das Dopaminsystem könnte dies das größere Abhängigkeitspotenzial von Methamphetamin erklären [16].…”

Section: Pharmakokinetikunclassified

Amphetamine und Crystal Meth: Epidemiologie, Symptomatik und Therapie konsumassoziierter Störungen

Quednow

Dürsteler²

2022

PSYCH up2date

View full text Add to dashboard Cite

Amphetaminkonsumstörungen, insbesondere im Zusammenhang mit dem substituierten Amphetaminderivat Methamphetamin („Crystal Meth“), treten im deutschsprachigen Raum zunehmend häufiger auf. Dieser Beitrag liefert eine aktuelle Übersicht zur Phänomenologie sowie zur Behandlung von Amphetaminkonsumstörungen. Darüber hinaus werden die Pharmakokinetik und -dynamik von Amphetamin und Methamphetamin detailliert besprochen.

show abstract

“…Others have implicated D2 downregulation in reversal learning by observing how repeated exposure to drugs that are misused impacted reversal learning. Reduced D2 density was reported in subjects with a history of stimulant misuse (Ballard et al, 2015;Kohno et al, 2021;Volkow et al, 2001), as were reversal learning impairments (Ersche et al, 2011;Pilhatsch et al, 2020). In non-human primates, a 31day methamphetamine regimen where the dose and number of daily injections were systematically increased resulted in concomitant impairments in reversal learning and D2 expression which were correlated (Groman et al, 2012).…”

Section: Dopamine and Reversal Learningmentioning

confidence: 99%

The Effects of Repeated Dopamine D2 Receptor Antagonism on D2 Receptor Expression and Behavioural Inflexibility

Highgate¹

View full text Add to dashboard Cite

Background: Reversal learning has been shown to improve as a function of dopamine D2 receptor expression, and manipulations that downregulated D2 expression also impaired behavioural flexibility. The possibility remains that an upregulation may facilitate reversal learning. Further, D2 receptor expression and reversal learning were compromised following repeated methamphetamine exposure. It stands to reason that restoration of receptor expression following methamphetamine exposure might prevent this impairment from occurring. Objectives: Develop a procedure for measuring reversal learning and determine whether repeated D2 receptor antagonism increases D2 receptor expression and improves behavioural flexibility in rats. Further, the possibility that this treatment would ameliorate behavioural inflexibility produced by prior methamphetamine exposure was examined. Methods: A task was developed to measure reversal learning. I systematically replicated an existing procedure, but then developed a novel procedure that focused on identifying a reasonable criterion for visual discrimination. To do this, male Sprague Dawley rats completed 25 days of visual discrimination. Various criteria requiring different levels of accuracy and persistence were retrospectively applied to the data and a single criterion was selected from these. The procedure was then extended to include three reversal tasks. In the next study, male Sprague-Dawley rats received repeated daily pretreatment with the dopamine D2 antagonist, eticlopride (0.0 or 0.3 mg/kg/day, IP, 14 days). Three days after treatment, whole-brain (minus olfactory bulbs and cerebellum) dopamine D2 receptor expression was measured using flow cytometry. Another cohort was exposed to the same regimen between the second and third reversal task to determine whether this treatment improved reversal learning. The final study was then conducted, the only difference from the previous study being that methamphetamine (0.0mg/kg or 2.0mg/kg, SC, 4 injections, 2 hours apart) was administered the day before eticlopride treatment commenced in order to produce behavioural inflexibility. Results: The criterion developed for the acquisition of visual discrimination was adopted for several reasons. First, the entire sample was able to meet the criterion. Second, the number of days to acquisition was equivalent irrespective of which visual cue served as the discriminative stimulus. Finally, accuracy was persistent both within and between test sessions. Importantly, therefore, these criteria eliminated confounds that might otherwise have been expected to impact reversal learning performance. The adjunct reversal tasks were typically completed within 2-5 test days, which was important since neuroadaptations can revert over time, and individual differences in performance were consistent across tasks. As expected, eticlopride treatment increased D2 receptor expression and improved reversal learning. Further, this improvement was predicted by baseline behavioural flexibility measures, such that, the improvement produced by repeated eticlopride treatment preferentially mpacted rats that were less behaviourally flexible prior to treatment. Methamphetamine treatment impaired reversal learning, but this impairment was prevented by repeated eticlopride treatment. Conclusions: Choice of criterion impacts behavioural performance in visual discrimination learning. D2 receptor expression is also a critical determinant of behavioural flexibility, irrespective of whether the discriminative stimulus is visual or spatial. Further, pre-existing, or experimentally produced behavioural inflexibility is sensitive to a treatment that upregulated D2 expression. Collectively, these findings support the critical role of D2 expression in reversal learning and suggest it is an effective target for facilitating behavioural flexibility.

show abstract

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment

Cited by 19 publications

References 113 publications

OCT Findings in Patients with Methamphetamine Use Disorder

OCT Findings in Patients with Methamphetamine Use Disorder

Amphetamine und Crystal Meth: Epidemiologie, Symptomatik und Therapie konsumassoziierter Störungen

The Effects of Repeated Dopamine D2 Receptor Antagonism on D2 Receptor Expression and Behavioural Inflexibility

Contact Info

Product

Resources

About