Persistent nigrostriatal dopaminergic abnormalities in ex-users of MDMA ('Ecstasy'): an 18F-dopa PET study.

Ecstasy (±3,4-methylenedioxymethamphetamine, MDMA) is a popular recreational drug with known serotonergic neurotoxicity. Its long-term effects on dopaminergic function are less certain. Studying the long-term effects of ecstasy is often confounded by concomitant polydrug use and the short duration of abstinence. We used (18)F-dopa positron emission tomography (PET) to investigate the long-term effects of ecstasy on nigrostriatal dopaminergic function in a group of male ex-recreational users of ecstasy who had been abstinent for a mean of 3.22 years. We studied 14 ex-ecstasy users (EEs), 14 polydrug-using controls (PCs) (matched to the ex-users for other recreational drug use), and 12 drug-naive controls (DCs). Each participant underwent one (18)F-dopa PET, cognitive assessments, and hair and urinary analyses to corroborate drug-use history. The putamen (18)F-dopa uptake of EEs was 9% higher than that of DCs (p=0.021). The putamen uptake rate of PCs fell between the other two groups, suggesting that the hyperdopaminergic state in EEs may be due to the combined effects of ecstasy and polydrug use. There was no relationship between the amount of ecstasy used and striatal (18)F-dopa uptake. Increased putaminal (18)F-dopa uptake in EEs after an abstinence of >3 years (mean) suggests that the effects are long lasting. Our findings suggest potential long-term effects of ecstasy use, in conjunction with other recreational drugs, on nigrostriatal dopaminergic functions. Further longitudinal studies are required to elucidate the significance of these findings as they may have important public health implications.

Acute effects of alcohol on memory: impact of emotional context and serial position.

Although the amnestic effects of alcohol in humans are well known, its effects on emotional memory are unclear. In this study, using a randomized double-blind placebo-controlled design, we examine narrative emotional episodic memory in healthy human female volunteers (n=32) who received either a single dose of alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented in either a neutral or emotional context. Memory was tested for gist and detail of the neutral elements 3days later in a surprise recognition test. Since alcohol modulates GABAergic neurotransmission and may exert its effects on emotion through the limbic system, we predicted that acute alcohol treatment would reduce the expected emotional memory-advantage for gist, leaving detail memory relatively unaffected. Furthermore, given previous findings showing that 'primacy' memory is enhanced by physiological arousal, we predicted that reduced arousal produced by alcohol would have the opposite effect and impair primacy memory relative to the middle or 'recency' sections of the narrative. Emotional arousal was expected to oppose this effect, so impaired primacy memory following alcohol was only expected in the neutral version of the narrative. Although there was a main effect of story phase (though not of story version), contrary to expectations, alcohol impaired primacy memory for emotionally encoded neutral material. The results suggest that under certain circumstances emotional context or physiological arousal make memories labile and susceptible to disruption through pharmacological manipulation during encoding.

Pharmacological manipulations of arousal and memory for emotional material: effects of a single dose of methylphenidate or lorazepam.

Benzodiazepines produce robust impairments of memory alongside global decreases in physiological and subjective arousal. Recently one benzodiazepine (triazolam) has been found to disproportionately impair memory for emotionally arousing material (Buchanan et al., 2003). The extent to which this effect may be mediated by the drug's sedative action is unclear. The present study aimed to assess how pharmacologically decreasing physiological arousal with a benzodiazepine and increasing arousal with a stimulant impact on memory for emotional material. A double-blind placebo controlled trial with 48 volunteers was used to investigate the effects of methylphenidate (40 mg) and Lorazepam (1.5 mg) on incidental memory for emotional material in Cahill and McGaugh's (1995) slide-story task. The slide-story was presented to participants administered either active drug or placebo and retrieval was assessed one week later. Methylphenidate produced stimulant effects and Lorazepam produced sedative effects. Significantly enhanced memory for emotional material was observed in participants given placebo, but not in those given either methylphenidate or Lorazepam. Despite producing opposite effects upon arousal, both methylphenidate and Lorazepam lessen the impact of emotionally arousing material on memory. The effects of Lorazepam add to a growing literature that benzodiazepines may exert their clinical, anxiolytic effects in part via altering emotionaL cognitive function.

Drugs, sweat, and fears: a comparison of the effects of diazepam and methylphenidate on fear conditioning.

RATIONALE: Classical conditioning of a fear response involves the formation of an association between a stimulus and an emotional response and can be seen as a basic form of emotional memory. While both benzodiazepines and stimulant drugs may influence the formation of episodic memories for emotional events, their effects on fear conditioning are less clear. OBJECTIVES: This study compared the effects of diazepam with methylphenidate on fear conditioning. MATERIALS AND METHODS: In a single-session between groups design with three conditions [placebo, diazepam (10 mg), and methylphenidate (40 mg)], classical conditioning of a skin conductance response to a visual stimulus previously paired with a 100-db white noise was tested in 45 healthy volunteers. RESULTS: Diazepam blocked fear conditioning, despite responses to the unconditioned aversive stimulus and neutral control stimulus being unimpaired. Conditioning remained intact after methylphenidate. Conditioned responses were not extinguished completely by the end of the experiment, and it was not possible to draw conclusions about the effects of the drugs on extinction. CONCLUSIONS: Although diazepam has well-documented amnesic effects, it has not been found to affect implicit forms of memory like perceptual and conceptual priming. As the present study found impaired fear conditioning after diazepam, it adds weight to recent findings that emotional memories are disproportionately impaired by the benzodiazepines.