Effects of 3,4-Methylenedioxymethamphetamine Administration on Retinal Physiology in the Rat

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a single MDMA administration in the rat electroretinogram (ERG). Wistar rats were administered MDMA (15 mg/kg) or saline and ERGs were recorded before (Baseline ERG), and 3 h, 24 h, and 7 days after treatment. A high temperature (HT) saline-treated control group was also included. Overall, significantly augmented and shorter latency ERG responses were found in MDMA and HT groups 3 h after treatment when compared to Baseline. Twenty-four hours after treatment some of the alterations found at 3 h, mainly characterized by shorter latency, tended to return to Baseline values. However, MDMA-treated animals still presented increased scotopic a-wave and b-wave amplitudes compared to Baseline ERGs, which were independent of temperature elevation though the latter might underlie the acute ERG alterations observed 3 h after MDMA administration. Seven days after MDMA administration recovery from these effects had occurred. The effects seem to stem from specific changes observed at the a-wave level, which indicates that MDMA affects subacutely (at 24 h) retinal physiology at the outer retinal (photoreceptor/bipolar) layers. In conclusion, we have found direct evidence that MDMA causes subacute enhancement of the outer retinal responses (most prominent in the a-wave), though ERG alterations resume within one week. These changes in photoreceptor/bipolar cell physiology may have implications for the understanding of the subacute visual manifestations induced by MDMA in humans

MDMA alters the response of the circadian clock to a photic and non-photic stimulus

3,4-Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) is a widely used recreational drug that damages serotonin 5-HT neurons in animals and possibly humans. Published literature has shown that the serotonergic system is involved in photic and non-photic phase shifting of the circadian clock, which is located in the suprachiasmatic nuclei. Despite the dense innervation of the circadian system by 5-HT and the known selective neurotoxicity of MDMA, little is known about the effects of MDMA on the circadian oscillator. This study investigated whether repeated exposure to the serotonin neurotoxin MDMA alters the behavioural response of the Syrian hamster to phase shift to the serotonin 5-HT1A/7 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT). This agonist was administered under an Aschoff Type I (CT8) and Aschoff Type II (ZT8) paradigm (5 mg/kg) and was given before and after treatment with MDMA (10, 15 and 20 mg/kg administered on successive days). Pre-treatment with MDMA significantly attenuated phase shifts to 8-OH-DPAT. We also tested the ability of the clock to phase shift to a photic stimulus after treatment with MDMA. A 15-min light pulse (mean lux 125 at CT14 or ZT14) was administered before and after treatment with MDMA. Phase shifts to a photic stimulus were significantly attenuated by pre-treatment with MDMA. Our study demonstrates that repeated exposure to MDMA may alter the ability of the circadian clock to phase shift to a photic and non-photic stimulus in the hamster. Disruption of circadian function has been linked with a variety of clinical conditions such as sleep disorders, mood, concentration difficulties and depression, consequently outlining the potential dangers of long-term ecstasy use

Fixation effects: do they exist in design problem solving?

Designing involves the use of a number of different types of knowledge which vary from abstract knowledge to knowledge about physical forms and their attributes. Previous research had demonstrated that pictorial representations of an example design presented as part of the statement of a design problem resulted in designs that exhibited the characteristics of the pictorial example. This effect was referred to as design fixation. However, subsequent attempts to replicate the effect were largely unsuccessful with what appeared to be fixation under some conditions being closely related to familiarity with existing examples of the design problem. There were, however, other differences between the two experiments, particularly in terms of the level of experience of the designers and the design discipline of the participents. In the experiment reported, familiarity with existing examples of solutions of a design problem was controlled by choosing an appropriate problem from the set of problems used in the original research and designers of the same discipline and level of experience were used together with designers from different disciplines. In addition to the pictorial representation of a design solution used in the original research, an additional pictorial example was included. The results demonstrated clear fixation effects when both the discipline of the designers and the pictorial example were the same as those used in the original experiment. However, no effect of the pictorial example occurred with designers of different disciplines or the other pictorial example for designers from any discipline. Possible reasons for these results are discussed, with particular reference to the effects of a match between the principles used in the design solution and the discipline of the designers.

MDMA induces Per1, Per2 and c-fos gene expression in rat suprachiasmatic nuclei

RATIONALE: ±3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a psychoactive drug that has marked effects on the serotonergic system. Serotonergic agonists are known to interact with the circadian pacemaker located in the suprachiasmatic nuclei (SCN). OBJECTIVES: Given changes reported in the behavioral activity rhythm followingMDMAtreatment, the effects ofMDMAon core clock gene (Per1, Per2) and c-fos expression were evaluated. METHODS: Male Long–Evans rats (n=72) were injected once with MDMA (5 mg/kg i.p.) or saline either at the middle of their ‘rest’ phase (Zeitgeber Time: ZT6) or the middle of their ‘active’ phase (Zeitgeber Time: ZT16) and killed at 30, 60, or 120 min posttreatment for gene expression analysis in the SCN using PCR. Behavioral rhythms of a separate group of rats (n=20) were measured following treatment at ZT16 while they were held in constant darkness for 10 days posttreatment. RESULTS: At ZT6, c-fos mRNA was significantly induced 120 min post-MDMA treatment but there were no significant changes in Per1 or Per2 mRNA expression. At ZT16, there were significant inductions of c-fos mRNA (30 and 60 min) and Per1 and Per2 mRNA (both 60 min) post-MDMA treatment. However, no differences in behavioral activity patterns were noted following MDMA treatment at ZT16. CONCLUSIONS: These data provide evidence that MDMA has time of day dependent actions on SCN functioning, as evident from its induction of core clock genes that are important for generating and maintaining circadian rhythmicity.Rowan P. Ogeil, David J. Kennaway, Mark D. Salkeld, Shantha M.W. Rajaratnam and Jillian H. Broadbea