There is a growing body of evidence that the main psychoactive ingredient of the recreational drug “ecstasy” (methylendioxymethamphetamine; MDMA) causes lasting changes to the serotonin system in both animals and humans, including the hippocampus (involved in memory) and the occipital lobe (involved in visual perception). Previous studies have often found memory deficits in ecstasy users. However, the results have been far from consistent across studies. None of the methods used to date have adequately isolated the hippocampal component of memory from the contribution of other brain regions. Three memory studies were conducted in this thesis to clarify which components and processes of memory are in deficit in ecstasy users.¶ In the first memory study, ecstasy users (n=32) did not differ from non-drug using controls (n=29) on implicit memory (automatic non-conscious retrieval, as revealed by a stem-completion task), or explicit memory (conscious recollection, as revealed by stem-cued recall). In the second memory study, no significant differences were found between ecstasy users (n=30) and non-drug using controls (n=34) on tests designed to clarify the findings on explicit memory, or on two standard neuropsychological tests of long-term memory (prose recall and Auditory Verbal Learning Test) that allowed greater use of elaborative processing at study. In the third memory study, a number of tests were applied that differed in their elaborative processing demands, including the California Verbal Learning Test, Visual Paired Associates, and Verbal Paired Associates. Ecstasy users (n=32) had poorer recall, and made less strategic use of elaborative processing compared to both cannabis-using controls (n=33) and non-drug using controls (n=33). Also, on a novel test of elaborative processing (“Verbal Triplet Associates”), both cannabis users and ecstasy users had memory deficits on the first trial, but only ecstasy users had a significant learning deficit over successive trials. On the basis of the localisation of the components and processes of memory in literature, it was concluded that long-term memory deficits in ecstasy users may reflect changes in elaborative processes localised in the frontal lobes, or global deficits, rather than just changes to the memory functions of the hippocampus.¶ With regard to visual perception, no studies have been published to date that have examined MDMA-related changes to the behavioural functioning of the occipital lobe in humans. In the current thesis, this was investigated using the tilt aftereffect illusion. In accordance with expectations, ecstasy users had a larger tilt aftereffect compared to non-drug using controls (n=34). Unexpectedly, this result was only obtained for a subset of 12 ecstasy users (out of n=30) who had not used amphetamines in the recent past. It was concluded that the results for ecstasy users who had not recently used amphetamines were consistent with the proposal that ecstasy-related serotonergic changes in the occipital lobe broaden the tuning bandwidth of orientation sensitive neurons, and that the recent use of amphetamines appears to counteract that effect.

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Originally developed as an anti-depressant and later available as a ‘party-pill’ in New Zealand, methylone is currently classed as an illegal drug. This is due to findings of its similarity in chemical structure to that of Ecstasy (MDMA). Methylone is a relatively new drug into which little research has been conducted. Consequently, no known study has investigated the long-term effects on behavioural development arising from exposure during adolescence. The present thesis therefore aimed to identify long-term effects of chronic adolescent exposure to methylone on adult anxiety-like behaviours. This was achieved by the use of 80 rats (40 males: 40 females) and exposing them to either a methylone or saline treatment for ten consecutive days. Two different treatment age groups (early versus late adolescence) were examined and to ensure adequate comparisons could be made, two control groups were utilised. All rats were tested during adulthood in four specifically selected anxiety-measure tests; the open-field, preference for the light side of a light-dark box, acoustic startle and responsiveness to the novel arm of a Y-maze. The results suggested methylone-exposed rats displayed more anxiolytic behaviours than saline-treated rats. In the open field methylone exposed rats exhibited less ambulation than controls and those treated in early adolescence defecated more while rats treated in late adolescence occupied the corners of the apparatus more exhibiting higher anxiety-like behaviours. Exploratory behaviours in the Y-maze were decreased in methylone-treated rats, and those exposed in early adolescence entered the novel arm less often. However, acoustic startle results suggested methylone-exposed rats were less anxious as evidenced by a lower startle amplitude than controls. Overall, the results suggested differences in anxiety-like behaviours between methylone-exposed rats and controls. It did not appear that being exposed to methylone in early adolescence resulted in vast differences in anxiety-like behaviours than if exposure began in late adolescence.