Pohlavní rozdíly v účincích kanabinoidů na působení extáze u myší

Title in English Gender differences in cannabinoid and ecstasy interacting effects in mice


Year of publication 2006
Type Article in Periodical
Magazine / Source Psychiatrie
MU Faculty or unit

Faculty of Medicine

Field Pharmacology and pharmaceutical chemistry
Keywords ecstasy; open field; behavioral sensitization
Description Both, ecstasy (MDMA) and cannabis are drugs abused very frequently and also consecutively simultaneously. As already shown repeated intake of ecstasy is able to induce development of so called behavioural sensitization (Robinson and Berridge, 1993) increasing its stimulatory effects. The present experiment was focused on a possible cross-sensitization to ecstasy with repeated application of cannabinoid CB1 receptor ligands with (agonist methanandamide) or without (AM 251) intrinsic activity. We also have considered possible gender differences which other authors had described in behavioural effects of ecstasy in mice. Evaluation of behavioural sensitization was based on changes of drug effects on mouse locomotor activity in the open field test measured by the device Actitrack (Panlab, S.L., Spain). Both, male and female mice of the same age were used. There was registered gradual significant decrease of locomotion in both, naive males and females as a consequence of habituation process on repeated exposition to the open field test. In animals treated with vehicle differences between males and females were shown. Males exhibit significantly (p < 0.05) lower locomotion in the 1st measurement after handling with vehicle treatment while females did not. Furthermore, while habituation in vehicle treated females resemble that one in the naive group, vehicle treated males instead exhibit significant (p < 0.05) increase in locomotion on the 2nd and 3rd open field test and habituation with decreased locomotion was apparent only on the last test when no significant difference occurred vs. vehicle treated females or naive animals of both genders. Development of significant behavioural sensitization was confirmed after repeated treatment with no significant gender differences found. Similar results were obtained after challenge dose of ecstasy given to animals pretreated repeatedly with CB1 receptor agonist methanandamide suggesting development of cross-sensitization. On the contrary the combined pretreatment with ecstasy and CB1 receptor antagonist AM 251 suppressed both development nor expression of behavioural sensitization to ecstasy similarly in both genders. Thus, our results so far did not confirm any gender difference in sensitivity to acute behavioural effect of ecstasy in mice which was described in rats where females seemed to be more vulnerable. Neither any gender differences were registered in development of sensitization after repeated treatment or in expression of sensitization provoked by challenge dose of ecstasy over a wash-out period. The expression of behavioural sensitization is considered as a crucial factor for incidence of relapses in withdrawal programmes for addicts. Presented results confirming behavioural sensitization to ecstasy effects as well as cross-sensitization with cannabinoid agonist may suggest an increasing vulnerability to addiction after intake of these drugs. On the other hand, the existence of antagonistic interaction between ecstasy and cannabinoid receptor antagonist inhibiting development of sensitization to ecstasy also shown might be important for choice of approaches to treatment of ecstasy abuse.
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