The onset of schizophrenia and the schizophrenomimetic effects of an N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, rarely occur during infancy and childhood, suggesting that schizophrenia-related neuron circuits and molecules in the brain might show an age-related response to an NMDA receptor antagonist. By using a DNA microarray technique, we have identified the developmentally...
A number of studies indicate that glutamatergic N-methyl-D-aspartate (NMDA) neurotransmission is disturbed in schizophrenia partly based on the findings that NMDA receptor antagonists such as phencyclidine (PCP) can reproduce a schizophrenia-like syndrome in both humans and rodents. This study investigated whether repeated administration of low doses of PCP can induce cognitive dysfunctions in...
The recreational drug 3,4-methylenedioxy-metamphetamine (MDMA; 'ecstasy') enhances serotonin and dopamine transmission. Repeated binge treatment with MDMA (5 mg/kg, 3 times daily, 3 h apart, once per week for 4 wk) was found to increase gene expression of S100B, a neurotrophic factor that modulates neuronal plasticity. Mutant mice overexpressing S100B were investigated to better understand how...
Ecstasy (3,4-methylenedioxymethylamphetamine; MDMA) is a popular club drug often taken with ethanol (EtOH). We recently found EtOH potentiated the psychomotor effects of MDMA in rats. This potentiation could reflect pharmacodynamic or/and pharmacokinetic processes. To test the latter hypothesis, rats were injected i.p. with 6.6 or 10 mg/kg MDMA with or without 1.5 g/kg EtOH, and were killed at...
The recreational drug ecstasy [3,4-methylenedioxymethamphetamine (MDMA)], has been found to selectively damage brain serotonin neurons in experimental animals, and probably in human MDMA users, but detailed morphometric analyses and parallel functional measures during damage and recovery are missing. Since there is evidence that serotonin regulates sleep, we have compared serotonergic markers...
Although numerous studies investigated the mechanisms underlying 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity, little is known about its long-term functional consequences on 5-HT neurotransmission in mice. This led us to evaluate the delayed effects of MDMA exposure on the 5-HT system, using in-vitro and in-vivo approaches in both 5-HTT wild-type and knock-out mice. Acute MDMA...
Abuse of 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) and methamphetamine (Meth or Speed) is a growing international problem with an estimated 250 million users of psychoactive drugs worldwide. It is important to demonstrate and understand the mechanism of neurotoxicity so potential prevention and treatment therapies can be designed. In this study rat primary cerebrocortical neuron...
MDMA causes selective depletion of serotonergic terminals in experimental animals and the consequent decrease in synaptic 5-HT may, inter alia, increase impulsivity. To study the effects of MDMA upon brain function, the behaviour of male Dark Agouti rats exposed to MDMA (15 mg/kg i.p.), two 5-HT1B agonists (CGS-12066A and CP-94,253, both 5 mg/kg i.p.) or saline were investigated in the...
Potent serotonin (5-HT) reuptake inhibitors are the only drugs that consistently exert a therapeutic action in obsessive-compulsive disorder (OCD). Given that some hallucinogens were reported to exert an anti-OCD effect outlasting their psychotomimetic action, possible modifications of neuronal responsiveness to 5-HT by LSD were examined in two rat brain structures: one associated with OCD, the...
The present study investigated the effects of chronic treatment with the atypical antipsychotic, clozapine, or the typical antipsychotic, haloperidol, on the stimulus properties of 2,5-dimethoxy-4-methylamphetamine ([-]-DOM) in rats trained to discriminate [-]-DOM (0.3 mg/kg; 75 min pre-treatment time) from vehicle. As compared with control values, treatment with clozapine (25 mg/kg.d) for 7 d...