Karel Šlais

Could piracetam potentiate behavioural effects of psychostimulants

Press and internet reports mention abuse of nootropic drug piracetam (PIR) in combination with psychostimulants methamphetamine (MET) or 4-methylenedioxymethamphetamine (MDMA). These combinations are believed to produce more profound desirable effects, while decreasing hangover. However, there is a lack of valid experimental studies on such drug-drug interactions in the scientific literature available. Our hypothesis proposes that a functional interaction exists between PIR and amphetamine psychostimulants (MET and MDMA) which can potentiate psychostimulant behavioural effects. Our hypothesis is supported by the results of our pilot experiment testing acute effects of drugs given to mice intraperitoneally (Vehicle, n=12; MET 2.5mg/kg, n=10; MDMA 2.5mg/kg, n=11; PIR 300 mg/kg, n=12; PIR+MET, n=12; PIR+MDMA, n=11) in the Open Field Test (Actitrack, Panlab, Spain). PIR given alone caused no significant changes in mouse locomotor/exploratory behaviour, whereas the same dose combined with either MET or MDMA significantly enhanced their stimulatory effects. Different possible neurobiological mechanism underlying drug-drug interaction of PIR with MET or MDMA are discussed, as modulation of dopaminergic, glutamatergic or cholinergic brain systems. However, the interaction with membrane phospholipids seems as the most plausible mechanism explaining PIR action on activities of neurotransmitter systems. Despite that our behavioural experiment cannot serve for explanation of the pharmacological mechanisms of these functional interactions, it shows that PIR effects can increase behavioural stimulation of amphetamine drugs. Thus, the reported combining of PIR with MET or MDMA by human abusers is not perhaps a coincidental phenomenon and may be based on existing PIR potential to intensify acute psychostimulant effects of these drugs of abuse.

P.5.023 The effects of cannabinoid CB1 receptor antagonist AM 251 on locomotor/exploratory behaviour and body weight in mice

The effects of the cannabinoid CB1 receptor antagonist AM 251 were assessed in adult, non-obese male mice. The changes in the behaviour recorded were aimed on locomotor/exploratory activity of mice in the open field test. The daily administration of AM 251 reduced dose-dependently and significantly body weight, while did not significantly affect locomotor/exploratpry activities neither after acute nor repeated administration.

Behavioural sensitization to methamphetamine stimulatory effects on locomotion: comparative study in mice and rats

In the Experiment 1, the significant stimulatory MET effects on mouse locomotion were apparent after the first dose (2.5 mg/kg), and the significantly increased effect was measured after the repeated administration. In the Experiment 2, MET at the doses of 2.5 or 5 mg/kg stimulated ambulation of rats in the open field test, however after the repeated administration these effects were decreased (insignificantly after the lower and significantly after the higher dose), however, in both groups stereotypic nose rubbing occurred (stereotypies are defined as one of possible signs of behavioural sensitization, too). In the Experiment 3, the significant stimulatory effect on ambulation of rats measured after the first dose of MET at the dose of 0.5 mg/kg was significantly higher after the 8th dose.

P.6.d.001 Are there gender or seasonal variabilities in mouse behavioral response to acute and chronic ecstasy

In this study we summarized and statistically processed results of four experiments of the same design proceeded during aproximately one year to evaluate gender differences on larger groups of mice treated with MDMA, and the females included were intact animals, but also ovariectomized females without or with estrogen substitution in the last experiment. A possibility of seasonal impact on behavioral variabilities was also evaluated.

Antiaggressive and anxiogenic effects of MDMA in aggressive and timid singly housed mice

We analyzed behavioural changes in 15 acts of 4 categories: sociable, timid, aggressive and locomotor. Mice were administered MDMA at the doses of 2.5 or 10 or 30 mg/kg, or saline in the equal amount of 1ml/kg, orally. Paired interactions were videotaped and ethological analysis was performed. In aggressive mice, MDMA in all tested doses caused highly significant inhibition of all aggressive activities with the significant increase of sociability and defensive-escape behaviour and at the highest dose also of walking. In timid mice, the most significant changes were in increase of defensive-escape behaviour and decrease of sociable activities; just the highest dose stimulated significantly walking.

P.5.015 The influence of felbamate on sensitization to methamphetamine behavioural effects in mice

Numerous studies refer to the important involvement of N-methyl-D-aspartate (NMDA) receptors in the development and expression of behavioural sensitization. Activating antiepileptic drugs of the 3rd generation, such as felbamate (FEL) also invoke psychotropic effects. They may possess attention-enhancing and antidepressant efficacy, cause anxiety, insomnia, and agitation. All pharmacological mechanisms of felbamate are not fully elucidated yet, but many of clinical effects may be related to the inhibition of NMDA currents. The present study focuses on investigation of felbamate influence on sensitization to methamphetamine effects on mouse locomotor/exploratory behaviour in the open field.We desribed prevention of expression of metamphetamine sensitization effect in the mice which received the drug challenge dose combined with felbamate.