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. 2024 Mar 8;14(3):265.
doi: 10.3390/brainsci14030265.

Dopamine Concentration Changes Associated with the Retrodialysis of Methylone and 3,4-Methylenedioxypyrovalerone (MDPV) into the Caudate Putamen

Robert Goldsmith  1 , Amal Aburahma  1 , Jon E Sprague  1
Affiliations

Dopamine Concentration Changes Associated with the Retrodialysis of Methylone and 3,4-Methylenedioxypyrovalerone (MDPV) into the Caudate Putamen

Robert Goldsmith et al. Brain Sci. .

Abstract

Structural modifications to synthetic psychoactive cathinones (SPCs), a class of drugs that contain a β-keto modification of the phenethylamine pharmacophore of amphetamine, induce differences in dopamine transporter (DAT) activity. Here, in vivo retrodialysis was utilized to deliver the SPCs 3,4-methylenedioxypyrovalerone (MDPV, a DAT inhibitor) or methylone (a DAT substrate) into the caudate putamen of male Sprague-Dawley rats. Dialysate samples were collected prior to and post drug administration, and temporal changes in dopamine concentration were quantified using HPLC-EC methods. Methylone elicited a 200% increase and MDPV a 470% increase in dopamine levels at the 10 min time point. The findings demonstrate that in vivo retrodialysis can be used to evaluate the effects of SPCs on neurotransmission in the brain.

Keywords: MDPV; bath salts; cathinone; dopamine; methylone; microdialysis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structures of methylone and MDPV. The phenethylamine portion of the molecule is indicated in blue.
Figure 2
Figure 2
Study design. (A) The microdialysis probe is capable of (1) being surgically implanted into a specific brain region; (2) delivering chemical stimulus (red), such as methylone and MDPV, and selectively measuring the analyte (black), such as dopamine, by using different types of dialysis membrane tips and rejecting non-targeted chemicals (blue). (B) The timeline for synthetic cathinone perfusion. Time zero indicates the beginning of the synthetic cathinone perfusion. After the surgical implantation of the microdialysis cannula, the cannula was allowed to equilibrate for 90 min before three baseline samples were collected and the perfusion medium was changed to aCSF containing methylone or MDPV (100 mM in aCSF). After the 15 min perfusion period, the perfusion medium was converted back to aCSF for the remaining collection period.
Figure 3
Figure 3
(A) Experimental extracellular dopamine concentration versus time plots for methylone and MDPV (100 mM) after direct infusion into the caudate putamen for 15 min (one-way ANOVA with a Student–Newman–Keuls post hoc test: F(25,104) = 10.413, p = 0.0001). (B) Experimental extracellular DOPAC concentration versus time plots for methylone and MDPV (100 mM) after direct infusion into the caudate putamen for 15 min. Each value is the mean ± SEM. (n = 5). * indicates significant differences between treatment groups. A single * represents p = 0.01 and ** represents p = 0.001. Average baseline levels of dopamine were 805.3 ± 16.9 pg/uL.
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