Dagmar Vršková

The effects of methamphetamine self-administration on behavioural sensitization in the olfactory bulbectomy rat model of depression

Depression is frequently comorbid with a drug addiction and may seriously complicate its treatment. Currently, there is no routinely used animal model to investigate this comorbidity. In this study the effect of repeated administration of methamphetamine on i.v. drug self-administration in an olfactory bulbectomy model of depression in rats was investigated in order to propose and validate a rat model of comorbid depression and addiction. Male Wistar rats were either olfactory-bulbectomized (OBX) or sham-operated. They subsequently underwent a methamphetamine sensitization regime, which consisted of daily i.p. injections of methamphetamine for a 14-d period; controls received Sal injections at the same frequency. The i.v. self-administration of methamphetamine (0.08 mg/kg in one infusion) paradigm on a fixed ratio schedule of reinforcement was performed using operant chambers. A significant decrease of the drug intake was recorded in sham-operated animals pretreated with methamphetamine when compared to the unpretreated group. This was not apparent in the OBX groups. Both groups of OBX animals exhibited a higher intake of methamphetamine compared to the corresponding sham-operated groups, thus confirming the hypothesis of higher drug intake in depressive conditions in this rodent model. The procedure of behavioural sensitization to methamphetamine decreased the number of self-administered drug doses per session in the sham-operated rats. It is hypothesized that this phenomenon resulted from increasing efficacy of the drug after behavioural sensitization caused by repeated methamphetamine intermittent administration.

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.2.22 Impact of behavioural sensitization to methamphetamine on i.v. selfadminitration of the drug in male and female rats

The female animals were already recorded to respond differently to methamphetamine (MET) abuse than males. This gender dissimilarity may be caused by the influence of estral cycles and different susceptibility to behavioural sensitization. In this study the model of i.v. self-administration of MET (or saline as control) combined with fourteen days (14 D) of intermittent pretreatment with MET (or saline) was used hypothesizing possible influence of behavioral sensitization to the drug on the spontaneous intake in i.v. self-administration sessions was used in male and female rats.

P.6.d.005 Impact of behavioural sensitization and estrogen levels on i.v. self-adminitration of methamphetamine in rats

All the animals experienced previously with effects of MET in the phase of pretreatment showed the lower self-administered intake of MET. This might indicate that MET produced more profound rewarding effects in rats previously sensitized to the drug. The female groups in estrus-like conditions self-administered higher doses of MET than male groups with the same treatment however the females in anestrus self-administererd even lower doses than males. This indicates certain enhancing effect of estrogens on MET addiction in laboratory rodent model which is in accordance with other findings from animal and human studies.