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- Kehr, J., et al.
(författare)
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Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats
- 2011
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Ingår i: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 164:8, s. 1949-1958
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE The designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACH Microdialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTS Mephedrone (3 mg·kg−1 s.c.) and (+)-amphetamine (1 mg·kg−1 s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg−1 s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t1/2 values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t1/2 values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONS The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties.
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- Kehr, J, et al.
(författare)
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Preferential Effects of Cariprazine on Counteracting the Disruption of Social Interaction and Decrease in Extracellular Dopamine Levels Induced by the Dopamine D3 Receptor Agonist, PD-128907 in Rats: Implications for the Treatment of Negative and Depressive Symptoms of Psychiatric Disorders
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 801641-
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Tidskriftsartikel (refereegranskat)abstract
- The negative and cognitive symptoms of schizophrenia and related disorders may be due to reduced dopaminergic tone in cortical brain areas. Alteration in the function of dopamine (DA) D3 receptors may play a role in this cortical hypofunctionality and underlie the deficits in social behaviors and cognitive functions in schizophrenia. Cariprazine is a potent DA D3-preferring D3/D2 receptor partial agonist that is approved for the treatment of schizophrenia and bipolar disorder. The objective of the study was to compare the abilities of cariprazine, aripiprazole (another DA receptor partial agonist with more D2 receptor preference), and ABT-925 (a selective DA D3 antagonist) to counteract the social deficit and neurochemical alterations induced by the D3 receptor-preferring agonist (+)-PD 128907 (PD) in rats. Administration of PD (0.16 mg/kg; s.c.) induced a marked (−72%) but short-lasting disruption of the defensive social aggregation behavior (huddling) in the first 10-min period. Cariprazine at all doses (0.1, 0.3, 1 mg/kg; p.o.) almost completely abolished the PD-induced disruption of huddling. Likewise, ABT-925 (3 mg/kg; p.o.) and to a lesser extent aripiprazole (20 mg/kg; p.o.) were effective in blocking the PD-induced disruption of huddling. As measured by microdialysis, the highest dose of cariprazine prevented a PD-induced decrease in DA levels (40–80 min post PD dose) in the medial prefrontal cortex (mPFC), whereas aripiprazole did not have a significant effect. ABT-925 significantly counteracted the effect of PD at 80 min post-dose. In the nucleus accumbens (nAcc) shell, the highest dose of cariprazine, as well as ABT-925 and aripiprazole, significantly reversed the PD-induced decrease in DA levels. Taken together, these data provide behavioral and in vivo neurochemical evidence for the preferential DA D3 receptor action of cariprazine in the rat. This property of cariprazine may offer therapeutic benefits against the cognitive deficits and negative/depressive symptoms of schizophrenia and related disorders.
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