Leoš Landa

Implication of NMDA receptors in behavioural sensitization to psychostimulants: A short review

Repeated administration of psychostimulants and other dependence-producing substances induces a substantial increase in behavioural responses, a phenomenon termed as behavioural sensitization. An increased response to the tested drug elicited by previous repeated administration of a different drug is called cross-sensitization. Behavioural sensitization is considered to be a relapse trigger in dependent subjects and animals sensitized by repeated administration of drugs of abuse, thus being considered a suitable model of craving, which is one of the very characteristic features of substance addiction. It has been described that apart from other actions, drugs of abuse exert their effect on the central nervous system by affecting glutamatergic transmissions, particularly via N-methyl-d-aspartate (NMDA) receptors. Thus, this review presents a brief overview of the impact of inhibition of the NMDA receptor system on sensitization, reflecting particularly on behavioural sensitization to psychostimulants. The text combines up-to-date information with time-proven facts and also compares data from the literature with the authors׳ recent findings concerning this topic.

Event-related potentials and their applications

Event-related potentials (ERPs) are characterised as brain voltage fluctuations associated in time with some physical or mental occurrence and represent a non-invasive technique reflecting activity of complex neuronal networks responsible for new stimuli detection and discriminative behaviour of individuals. ERPs are measured using electroencephalography and their applications became widespread since 1960s of the last century. This review brings introduction into the ERPs technique and characteristics of the individual ERPs components (particularly wave P300, Contingent Negative Variation, Mismatch Negativity and Bereitschaftspotential). In addition, it summarizes changes of ERPs associated with neurologic and psychiatric diseases and finally, it mentions possible use of this approach for purposes of experimental psychology.

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.6.d.010 Acute and repeated exposure to methamphetamine changes expression of CB1 receptor in mesencephalon of the mouse brain

Real-time PCR results showed increased CB1 mRNA expression after both methamphetamine and methanandamide first doses followed by decrease in CB1 mRNA expression observed after the challenge dose of methamphetamine, i.e. in sensitized animals.

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.

The use of cannabinoids in animals and therapeutic implications for veterinary medicine: a review

This review sets out to comprehensively summarise well known facts concerning properties of cannabinoids, their mechanisms of action, role of cannabinoid receptors and their classification. It outlines the main pharmacological effects of cannabinoids in laboratory rodents and it also discusses examples of possible beneficial use in other animal species (ferrets, cats, dogs, monkeys) that have been reported in the scientific literature. Finally, the article deals with the prospective use of cannabinoids in veterinary medicine.

P.6.d.006 Repeated exposure to methamphetamine and methanandamide changes relative expression of D1 receptor in mouse midbrain

The results of the behavioural investigation showed: a) significant stimulatory influence of methamphetamine after the acute administration, b) development of sensitization to methamphetamine after its repeated treatment, c) development of cross-sensitization to methamphetamine after repeated pre-treatment with CB1 receptor agonist methanandamide. Real-time PCR results showed increased D1 mRNA expression both in animals sensitized to methamphetamine and in animals cross-sensitized to methamphetamine (repeatedly pre-treated with methanandamide).

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.