Publications (5) View all
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Article: Long-term cognitive and neurochemical effects of "bath salt" designer drugs methylone and mephedrone.
Bjørnar den Hollander, Stanislav Rozov, Anni-Maija Linden, Mikko Uusi-Oukari, Ilkka Ojanperä, Esa R Korpi[show abstract] [hide abstract]
ABSTRACT: INTRODUCTION/AIMS: The use of cathinone-derivative designer drugs methylone and mephedrone has increased rapidly in recent years. Our aim was to investigate the possible long-term effects of these drugs on a range of behavioral tests in mice. Further, we investigated the long-term effects of these drugs on brain neurochemistry in both rats and mice. METHODS: We treated animals with a binge-like regimen of methylone or mephedrone (30mg/kg, twice daily for 4days) and, starting 2weeks later, we performed behavioral tests of memory, anxiety and depression and measured brain levels of dopamine (DA), serotonin (5-HT), their metabolites and norepinephrine (NE). 5-HT and DA transporter (5-HTT, DAT) levels were also measured in rats by [(3)H]paroxetine and [(3)H]mazindol binding. RESULTS: Mephedrone reduced working memory performance in the T-maze spontaneous alternation task but did not affect neurotransmitter levels aside from a 22% decrease in striatal homovanillic acid (HVA) levels in mice. Methylone had little effect on behaviour or neurotransmitter levels in mice but produced a widespread depletion of 5-HT and 5-HTT levels in rats. CONCLUSIONS: Both methylone and mephedrone appeared to have a long-term effect on either behavioral or biochemical gauges of neurotoxicity in rodents.Pharmacology Biochemistry and Behavior 10/2012; · 2.53 Impact Factor -
Article: The Effects of Ecstasy (MDMA) on Brain Serotonin Transporters Are Dependent on Age-of-First Exposure in Recreational Users and Animals.
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ABSTRACT: Little is known on the effects of ecstasy (MDMA, a potent 5-HT-releaser and neurotoxin) exposure on brain development in teenagers. The objective of this study was to investigate whether in humans, like previous observations made in animals, the effects of MDMA on the 5-HT system are dependent on age-of-first exposure. 5-HT transporter (SERT) densities in the frontal cortex and midbrain were assessed with [(123)I]β-CIT single photon emission computed tomography in 33 users of ecstasy. Subjects were stratified for early-exposed users (age-at-first exposure 14-18 years; developing brain), and late-exposed users (age-at-first exposure 18-36 years; mature brain). In parallel, we investigated the effects of age experimentally with MDMA in early-exposed (adolescent) rats and late-exposed (adult) rats using the same radioligand. On average, five years after first exposure, we found a strong inverse relationship, wherein age-at-first exposure predicted 79% of the midbrain SERT variability in early (developing brain) exposed ecstasy users, whereas this was only 0.3% in late (mature brain) exposed users (p = 0.007). No such effect was observed in the frontal cortex. In rats, a significant age-BY-treatment effect (p<0.01) was observed as well, however only in the frontal cortex. These age-related effects most likely reflect differences in the maturational stage of the 5-HT projection fields at age-at-first exposure and enhanced outgrowth of the 5-HT system due to 5-HT's neurotrophic effects. Ultimately, our findings stress the need for more knowledge on the effects of pharmacotherapies that alter brain 5-HT levels in the pediatric population.PLoS ONE 01/2012; 7(10):e47524. · 4.09 Impact Factor -
Article: Preliminary evidence of hippocampal damage in chronic users of ecstasy.
Bjørnar den Hollander, Marieke Schouw, Paul Groot, Henk Huisman, Matthan Caan, Frederik Barkhof, Liesbeth Reneman[show abstract] [hide abstract]
ABSTRACT: Various studies have shown that ecstasy (3,4-methylenedioxymethamphetamine) users display significant memory impairments, whereas their performance on other cognitive tests is generally normal. The hippocampus plays an essential role in short-term memory. There are, however, no structural human data on the effects of ecstasy on the hippocampus. The objective of this study was to investigate whether the hippocampal volume of chronic ecstasy users is reduced when compared with healthy polydrug-using controls, as an indicator of hippocampal damage. The hippocampus was manually outlined in volumetric MRI scans in 10 male ecstasy users (mean age 25.4 years) and seven healthy age- and gender-matched control subjects (21.3 years). Other than the use of ecstasy, there were no statistically significant differences between both groups in exposure to other drugs of abuse and alcohol. The ecstasy users were on average drug-free for more than 2 months and had used on average 281 tablets over the past six and a half years. The hippocampal volume in the ecstasy using group was on average 10.5% smaller than the hippocampal volume in the control group (p=0.032). These data provide preliminary evidence that ecstasy users may be prone to incurring hippocampal damage, in line with previous reports of acute hippocampal sclerosis and subsequent atrophy in chronic users of this drug.Journal of neurology, neurosurgery, and psychiatry 03/2011; 83(1):83-5. · 4.87 Impact Factor -
Article: [Designer drugs in Finland].
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ABSTRACT: Designer drugs are synthetic psychotropic drugs which are marketed as "legal drugs". Their emergence, rapid spreading and unpredictable effects have challenged the health and substance abuse care. The slow process of classification of an abusable drug has provided too many possibilities for spreading the designer drugs. Once a certain substance receives an illegal drugs classification, dealers and users usually move to another, slightly different molecule that is still legal. In Finland, the Narcotics Act has been amended to the effect that the addition of a new substance to the illegal drug list does not require an amendment to the law.Duodecim; lääketieteellinen aikakauskirja 01/2011; 127(19):2027-36. -
Article: μ-Opioid receptors in the nucleus accumbens shell region mediate the effects of amphetamine on inhibitory control but not impulsive choice.
Joost Wiskerke, Dustin Schetters, Inge E van Es, Yvar van Mourik, Bjørnar R O den Hollander, Anton N M Schoffelmeer, Tommy Pattij[show abstract] [hide abstract]
ABSTRACT: Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of impulsivity, the five-choice serial reaction time task and the delayed-reward task, providing measures of inhibitory control and impulsive choice, respectively. We focused on the role of opioid receptor activation in amphetamine-induced impulsivity as there is ample evidence indicating an important role for endogenous opioids in several behavioral and neurochemical effects of amphetamine. Results showed that amphetamine-induced inhibitory control deficits were dose-dependently attenuated by the preferential μ-opioid receptor antagonist naloxone, but not by the selective δ-opioid receptor antagonist naltrindole or κ-opioid receptor antagonist nor-BNI (nor-binaltorphimine dihydrochloride). In contrast, naloxone did not affect amphetamine-induced improvements in impulsive decision making. Naloxone also completely prevented inhibitory control deficits induced by GBR 12909 [1-(2-[bis(4-fluorophenyl)methoxy] ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride], a selective dopamine transporter inhibitor. Intracranial infusions of naloxone, the selective μ-opioid receptor antagonist CTAP (H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)), morphine, and the selective μ-opioid receptor agonist DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin acetate salt) revealed that μ-opioid receptor activation in the shell rather than the core subregion of the nucleus accumbens (NAc) modulates inhibitory control and subserves the effect of amphetamine thereon. Together, these results indicate an important role for NAc shell μ-opioid receptors in the regulation of inhibitory control, probably via an interaction between these receptors and the mesolimbic dopamine system.Journal of Neuroscience 01/2011; 31(1):262-72. · 7.11 Impact Factor
