BACKGROUND AND PURPOSEThe 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 APPROACHMicrodialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTSMephedrone (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 IMPLICATIONSThe 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.

Background and purpose:Experimental and clinical data suggest that extracts of Ginkgo biloba improve cognitive function. However, the neurochemical correlates of these effects are not yet fully clarified. The purpose of this study was to examine the effects of acute and repeated oral administration of the standardized extract EGb 761 ® on extracellular levels of dopamine, noradrenaline and serotonin (5-HT), and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC) and striatum of conscious rats. ) had no effect on monoamine levels. However, following chronic (100 mg·kg -1 /14 days/once daily) treatment, the same dose significantly increased extracellular dopamine and noradrenaline levels, while 5-HT levels were unaffected. Chronic treatment with EGb 761 showed dose-dependent increases in frontocortical dopamine levels and, to a lesser extent, in the striatum. The extracellular levels of HVA and DOPAC were not affected by either acute or repeated doses. Treatment with the main constituents of EGb 761 revealed that the increase in dopamine levels was mostly caused by the flavonol glycosides and ginkgolide fractions, whereas bilobalide treatment was without effect. Conclusions and implications:The present results demonstrate that chronic but not acute treatment with EGb 761 increased dopaminergic transmission in the PFC. This finding may be one of the mechanisms underlying the reported effects of G. biloba in improving cognitive function. Pharmacology (2010) 159, 659-668; doi:10.1111/j.1476-5381.2009.00580.x; published online 25 January 2010 British Journal ofKeywords: Ginkgo biloba; microdialysis; monoamines; dopamine; noradrenaline; serotonin; prefrontal cortex; cognitive function Abbreviations: CMC, carboxymethylcellulose; DOPAC, 3,4-dihydroxyphenylacetic acid; HPLC, high-performance liquid chromatography; HVA, homovanillic acid; MAO, monoamine oxidase; PFC, prefrontal cortex IntroductionExtracts of Ginkgo biloba (EGb 761 ® ) have been shown to exert beneficial effects as cognitive enhancers in ageing, anti-stress agents and in therapy of age-related neurological disorders such as Alzheimer's disease (see DeFeudis and Drieu, 2000;DeFeudis, 2003;DeKosky and Furberg, 2008). A number of clinical studies have demonstrated that extracts of G. biloba, and particularly the standardized extract EGb 761, could ameliorate cognitive defects associated with mild to moderate Alzheimer's disease (Andrieu et al., 2003;Kanowski and Hoerr, 2003;Mazza et al., 2006;Napryeyenko et al., 2007;Scripnikov et al., 2007;Dodge et al., 2008). However, a recent Cochrane review on published randomized, double-blind, clinical trials has found that the use of G. biloba extracts was safe but the evidence for a significant benefit in people with dementia or cognitive impairment was inconsistent and unconvincing (Birks and Grimley Evans, 2007). In addition, a randomized, double-blind, placebo-controlled clinical study on 3069 volunteers aged 75 years or older receiving EGb 761 a...

The role of the ATP-gated receptor, P2X(7), has been evaluated in the unilateral 6-OHDA rat model of Parkinson's disease using the P2X(7) competitive antagonist A-438079. Nigral P2X(7) immunoreactivity was mainly located in microglia but also in astroglia. A-438079 partially but significantly prevented the 6-OHDA-induced depletion of striatal DA stores. However, this was not associated with a reduction of DA cell loss. Blockade of P2X(7) receptors may represent a novel protective strategy for striatal DA terminals in Parkinson's disease and warrants further future investigation.

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