BACKGROUND
the use of illicit drugs such as  <dig> -methylenedioxymethamphetamine  has increased among young people in europe and north america  <cit>  over the past years.
concern has been expressed about the increasing popularity of this stimulant drug and its association with certain youth subcultures, in particular the dance music scene  <cit> .
the widespread use of ecstasy is due to its ability to produce feelings of euphoria and energy and a desire to socialize.
in addition to these positive effects, mdma is relatively inexpensive to produce and purchase and has the reputation of being safer than other recreational drugs.
yet there is mounting evidence that ecstasy does not deserve this rosy reputation.
in fact, evidence has been accumulated, both in human and animal studies, that shows the possible risks engendered by the consumption of mdma  <cit> .
in many reviews these risks are extensively discussed in terms of toxicity, psychopathology and abuse potential associated with acute and chronic use  <cit> .
it is also clear that some environmental conditions can influence the toxicity of this drug in humans.
for example, one of the consequences of the use of ecstasy at "raves" is the increase in body temperature that is due to a direct action of the drug on the thermoregulatory system, to the intense muscular activity and to elevated environmental temperatures.
in addition, evidence from research done with an assortement of animal species from rodents to non-human primates, has shown that ecstasy is neurotoxic  <cit> .
in fact, it has been shown that ecstasy is able to cause serotonergic  <cit>  and dopaminergic  <cit>  neuronal toxicity in every animal species tested and short-term changes in the noradrenergic system  <cit> .
it has also been repeatedly demonstrated that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of mdma in humans where ecstasy use is positively correlated with absolute power changes in some frequency bands  <cit> .
one of the questions which need addressing by research is how other factors typical of the "rave scene", such as sensorial auditory  stimuli, can affect higher neural functions and in particular electrocortical activity  <cit> .
based on these evidences, we investigated whether sound stimulation affects electrocorticographic changes of total spectrum power induced by simultaneous administration of low doses of mdma in rats.
RESULTS
short term evaluation
in the short term evaluation set of experiments, the administration of saline did not induce any modification in ecog total spectrum power values in rats exposed to acoustic stimulation with respect to non-stimulated animals .
the systemic administration of mdma  was not able to modify ecog total spectrum power values with respect to saline treated animals.
on the contrary, in mdma-treated  animals, acoustic stimulation induced a significant reduction in ecog total spectrum power with respect to saline -sound off , saline -sound on  and mdma-sound off  treated animals .
mdma administered at the dose of  <dig> mg/kg -sound off induced a marked decrease of ecog total spectrum power in comparison to control  and mdma  -sound off  group.
sensorial stimulation enhanced ecog activation with respect to the control , mdma  -sound off/sound on  and mdma  <dig> mg/kg -sound off  .
in all the experiments the effects of mdma became evident within 1– <dig> min after the treatment.
long term evaluation
in the long term evaluation set of experiments, animals treated with saline-sound off did not show any change of ecog total spectrum power values with respect to rats treated with saline-sound on, mdma  <dig> mg/kg -sound off,  <dig> mg/kg -sound off and mdma  <dig> mg/kg -sound on.
these effects lasted 120– <dig> min after administration and the evaluation of ecog total spectrum power  <dig> h,  <dig> and  <dig> days after treatment, did not evidence any difference with respect to the control  group .
on the contrary, the long term evaluation of ecog parameters in animals treated with the higher dose of mdma  -sound on, evidenced a significant decrease of total spectrum power values  <dig> h,  <dig> and  <dig> days after treatment with respect to the control , saline-sound on , mdma  -sound off /-sound on  and to mdma  -sound off  treated animals.
discussion
the most relevant finding in these experiments is that rats exposed to an acoustic stimulation  that per se does not modify the electrocortical parameters evaluated, show, after the administration of mdma, a marked increase in electrocortical activity with respect to animals treated with the same dose of drug but in absence of sensorial stimulation.
in particular, the lower dose of mdma used  was not able to modify electrocortical parameters considered only in absence of sound stimulation when, in the same treatment group, the administration of sound significantly reduced the ecog power.
in addition, the administration of a single dose of  <dig> mg/kg of mdma, induced , significant stimulation of the electrical activity of the brain cortex lasting for five days after the administration of the drug.
the mechanisms underlying these differences in the duration of effects of similar treatments  remain obscure; however, one might speculate that the higher  dosage of mdma used in the present study might have produced a comparable cross-sensitisation of the animals to react with higher  electrocortical activity to acoustic stimuli.
also the neurochemical basis of the synergism between noise exposure and mdma call for more in-depth studies aimed at disclosing the fine mechanisms underlying this enhancement.
in fact it has been well demonstrated that exposure to mdma produces in mice long-lasting eeg changes and latent brain hyperexcitability, as shown by persistent changes in baseline and activated eeg, seizure facilitation and latent metabolic hyperactivity and that these effects are concomitant with monoamine depletion within limbic regions and basal ganglia  <cit> , and studies focused on the basal ganglia circuitry  <cit> , evidentiate that neurotoxicity affect either serotonin  or/and dopamine  nerve endings.
indeed, the data available in literature mainly relate to tests on animals, in which the short- and long-term neurotoxic effects of mdma are evaluated following administration of high doses  which in some studies are repeated for as long as seven consecutive days  <cit> .
it has been also well demonstrated that acoustic stimulation combined with ecstasy produces a selective enhancement of neurotoxicity   <cit>  and cardiotoxicity  <cit>  in the mouse.
despite the increasimg number of evidences demonstrating the synergism between noise and mdma in inducing toxical effects, it is very difficult to indicate the mechanism underliyng these effects.
the persistence of the electrocortical effects need in-depht studies aimed at elucidating the link between serotonergic and acoustic systems and the biochemical changes induced by mdma and noise – treatment.
our experiments evaluated the effect on animals of low doses of mdma associated with sensorial  comparable to those occurring in human life within young people's social gatherings of the "rave" or "techno" type, whose habitués are known to regularly take this type of drug, especially during parties chiefly characterised by strong sensorial stimulations.
CONCLUSIONS
taken together, our data demonstrate that mdma, even taken in low doses, is capable of reducing the total power of the electrocorticographic spectrum, a parameter for the evaluation of the activation of the telencephalic cortex, in rats.
in our experimental conditions this activation spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to mdma, the animals are exposed to acoustic stimulation.
we can therefore state that the effects of this drug could be potentiated by relatively common environmental factors and stress the potential danger for man of substances that have been so "popularly" accepted as relatively "safe" owing to their "short term" effects.

 the use of illicit drugs such as -methylenedioxymethamphetamine has increased among young people in europe and north america over the past years. concern has been expressed about the increasing popularity of this stimulant drug and its association with certain youth subcultures, in particular the dance music scene. the widespread use of ecstasy is due to its ability to produce feelings of euphoria and energy and a desire to socialize. in addition to these positive effects, mdma is relatively inexpensive to produce and purchase and has the reputation of being safer than other recreational drugs. yet there is mounting evidence that ecstasy does not deserve this rosy reputation. in fact, evidence has been accumulated, both in human and animal studies, that shows the possible risks engendered by the consumption of mdma. in many reviews these risks are extensively discussed in terms of toxicity, psychopathology and abuse potential associated with acute and chronic use. it is also clear that some environmental conditions can influence the toxicity of this drug in humans. for example, one of the consequences of the use of ecstasy at "raves" is the increase in body temperature that is due to a direct action of the drug on the thermoregulatory system, to the intense muscular activity and to elevated environmental temperatures. in addition, evidence from research done with an assortement of animal species from rodents to non-human primates, has shown that ecstasy is neurotoxic. in fact, it has been shown that ecstasy is able to cause serotonergic and dopaminergic neuronal toxicity in every animal species tested and short-term changes in the noradrenergic system. it has also been repeatedly demonstrated that electroencephalography may be a cheap and effective tool for examining neurotoxic effects of mdma in humans where ecstasy use is positively correlated with absolute power changes in some frequency bands. one of the questions which need addressing by research is how other factors typical of the "rave scene", such as sensorial auditory stimuli, can affect higher neural functions and in particular electrocortical activity. based on these evidences, we investigated whether sound stimulation affects electrocorticographic changes of total spectrum power induced by simultaneous administration of low doses of mdma in rats.  short term evaluation in the short term evaluation set of experiments, the administration of saline did not induce any modification in ecog total spectrum power values in rats exposed to acoustic stimulation with respect to non-stimulated animals. the systemic administration of mdma was not able to modify ecog total spectrum power values with respect to saline treated animals. on the contrary, in mdma-treated animals, acoustic stimulation induced a significant reduction in ecog total spectrum power with respect to saline -sound off, saline -sound on and mdma-sound off treated animals. mdma administered at the dose of mg/kg -sound off induced a marked decrease of ecog total spectrum power in comparison to control and mdma -sound off group. sensorial stimulation enhanced ecog activation with respect to the control, mdma -sound off/sound on and mdma mg/kg -sound off. in all the experiments the effects of mdma became evident within 1– min after the treatment. long term evaluation in the long term evaluation set of experiments, animals treated with saline-sound off did not show any change of ecog total spectrum power values with respect to rats treated with saline-sound on, mdma mg/kg -sound off, mg/kg -sound off and mdma mg/kg -sound on. these effects lasted 120– min after administration and the evaluation of ecog total spectrum power h, and days after treatment, did not evidence any difference with respect to the control group. on the contrary, the long term evaluation of ecog parameters in animals treated with the higher dose of mdma -sound on, evidenced a significant decrease of total spectrum power values h, and days after treatment with respect to the control, saline-sound on, mdma -sound off /-sound on and to mdma -sound off treated animals. discussion the most relevant finding in these experiments is that rats exposed to an acoustic stimulation that per se does not modify the electrocortical parameters evaluated, show, after the administration of mdma, a marked increase in electrocortical activity with respect to animals treated with the same dose of drug but in absence of sensorial stimulation. in particular, the lower dose of mdma used was not able to modify electrocortical parameters considered only in absence of sound stimulation when, in the same treatment group, the administration of sound significantly reduced the ecog power. in addition, the administration of a single dose of mg/kg of mdma, induced, significant stimulation of the electrical activity of the brain cortex lasting for five days after the administration of the drug. the mechanisms underlying these differences in the duration of effects of similar treatments remain obscure; however, one might speculate that the higher dosage of mdma used in the present study might have produced a comparable cross-sensitisation of the animals to react with higher electrocortical activity to acoustic stimuli. also the neurochemical basis of the synergism between noise exposure and mdma call for more in-depth studies aimed at disclosing the fine mechanisms underlying this enhancement. in fact it has been well demonstrated that exposure to mdma produces in mice long-lasting eeg changes and latent brain hyperexcitability, as shown by persistent changes in baseline and activated eeg, seizure facilitation and latent metabolic hyperactivity and that these effects are concomitant with monoamine depletion within limbic regions and basal ganglia, and studies focused on the basal ganglia circuitry, evidentiate that neurotoxicity affect either serotonin or/and dopamine nerve endings. indeed, the data available in literature mainly relate to tests on animals, in which the short- and long-term neurotoxic effects of mdma are evaluated following administration of high doses which in some studies are repeated for as long as seven consecutive days. it has been also well demonstrated that acoustic stimulation combined with ecstasy produces a selective enhancement of neurotoxicity and cardiotoxicity in the mouse. despite the increasimg number of evidences demonstrating the synergism between noise and mdma in inducing toxical effects, it is very difficult to indicate the mechanism underliyng these effects. the persistence of the electrocortical effects need in-depht studies aimed at elucidating the link between serotonergic and acoustic systems and the biochemical changes induced by mdma and noise – treatment. our experiments evaluated the effect on animals of low doses of mdma associated with sensorial comparable to those occurring in human life within young people's social gatherings of the "rave" or "techno" type, whose habitués are known to regularly take this type of drug, especially during parties chiefly characterised by strong sensorial stimulations.  taken together, our data demonstrate that mdma, even taken in low doses, is capable of reducing the total power of the electrocorticographic spectrum, a parameter for the evaluation of the activation of the telencephalic cortex, in rats. in our experimental conditions this activation spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to mdma, the animals are exposed to acoustic stimulation. we can therefore state that the effects of this drug could be potentiated by relatively common environmental factors and stress the potential danger for man of substances that have been so "popularly" accepted as relatively "safe" owing to their "short term" effects. 
acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug. we investigated the effects of low doses of mdma in vivo using wistar rats in the absence of acoustic stimulation demonstrating that ecstasy is able to induce a significant activation of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to mdma, the animals are exposed to acoustic stimulation. our data demonstrate that low doses of mdma are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties. -methylenedioxymethamphetamine is known for its toxicological, psychopathological and abuse potential.
 -methylenedioxymethamphetamine is known for its toxicological, psychopathological and abuse potential. some environmental conditions, e.g. acoustic stimulation typical of the "rave scene" can influence the toxicity of this drug.  we investigated the effects of low doses of mdma in vivo using wistar rats in the absence of acoustic stimulation demonstrating that ecstasy is able to induce a significant activation of the telencephalic cortex that spontaneously reverts in the absence of sensorial stimuli, whereas it persists for several days if, in addition to mdma, the animals are exposed to acoustic stimulation.  our data demonstrate that low doses of mdma are able to reduce electrocortical total power, and that this effect is potentiated by sensorial stimuli commonly present in certain environments, such as rave parties. 