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A consistent effect of repeated exposure to 3,4 methylenedioxymethamphetamine (MDMA) is a decrease in the tissue levels of serotonin (5-HT). A variety of behavioural and neurochemical tests were conducted to determine whether the tissue deficits were accompanied by an increased sensitivity of the 5-HT1a autoreceptor. Tests were conducted 2 weeks following MDMA exposure (four injections of 10.0 mg/kg, IP, administered at 2-h intervals in a single day). The response to the 5-HT1a agonist, 8-OHDPAT (0.003-0.5 mg/kg, SC), was assessed using lower lip retraction (LLR), hypoactivity, and 5-hydroxytryptophan (5-HTP) accumulation following decarboxylase inhibition. The 8-OHDPAT produced a dose-dependent increase in LLR and hypoactivity, but these effects were comparable for MDMA and saline pretreated groups. MDMA decreased tissue levels of 5-HT and the accumulation of 5-HTP, but these effects were not reflected in the changes in autoreceptor sensitivity. The data suggest that the decrease in tissue levels of 5-HT produced by MDMA is accompanied by a decrease in tryptophan hydroxylase activity but cannot be explained by supersensitivity of the 5-HT1a autoreceptor.

In the present study, we explored the role of faces in oculomotor inhibition of return (IOR) using a tightly controlled spatial cuing paradigm. We measured saccadic response latency to targets following peripheral cues that were either faces or objects of lesser sociobiological salience. A recurring influence from cue content was observed across numerous methodological variations. Faces versus other object cues briefly reduced saccade latencies toward subsequently presented targets, independently of attentional allocation and IOR. The results suggest a short-lived priming effect or social facilitation effect from the mere presence of a face. In the present study, we further showed that saccadic responses were unaffected by face versus nonface objects in double-cue presentations. Our findings indicate that peripheral face cues do not influence attentional orienting processes involved in IOR any differently from other objects in a tightly controlled oculomotor IOR paradigm.Keywords Eye movements and visual attention . Cognitive and attentional control . Inhibition of return . Face perception Attention allows for the selective processing of one source of information over other simultaneously available sources. Stolz (1996) demonstrated that the spatial orienting of exogenous visual attention can be influenced by content at peripheral locations. Using Posner's (1980) spatial cuing paradigm, the semantic relation of peripherally presented cue words to a context word was shown to influence the disengagement of attention. Subsequent research has also shown that emotional valence of cues can influence attentional disengagement (e.g

These data suggest that the initial reinforcing effects of MDMA are modulated by 5-HT1A and/or 5-HT1B receptor mechanisms. The potential impact of these changes on the DAergic response relevant to self-administration and a possible role in conditioned reinforcement pertaining to acquisition of self-administration are discussed.

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As is the case with other drugs of abuse, a proportion of ecstasy users develop symptoms consistent with a substance use disorder (SUD). In this paper, we propose that the pharmacology of MDMA, the primary psychoactive component of ecstasy tablets, changes markedly with repeated exposure and that neuroadaptations in dopamine and serotonin brain systems underlie the shift from MDMA use to MDMA misuse in susceptible subjects. Data from both the human and laboratory animal literature are synthesized to support the idea that (1) MDMA becomes a less efficacious serotonin releaser and a more efficacious dopamine releaser with the development of behaviour consistent with an SUD and (2) that upregulated serotonin receptor mechanisms contribute to the development of the MDMA SUD via dysregulated inhibitory control associated with the trait of impulsivity.

Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms.