The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the...
In despite the similarity of mechanisms of action between both selective serotonin reuptake inhibitors (SSRI) and MDMA (main compound of "Ecstasy") there are relatively few reports on the effects of the later on animal models of depression. There are many animal models designed to create or to assess depression. Mild chronic stress (MCS) is a procedure designed to create depression. MCS...
Deficits in pre-pulse inhibition (PPI-indicative of psychosis in humans) can be replicated in rats using the NMDA receptor antagonist phencyclidine (PCP). Ultrasonic vocalisations (USVs) produced by rats in response to acoustic startle are indicative of heightened anxiety; here we tested the predictive validity of USVs as an indicator of PPI. Male juvenile Sprague-Dawley rats (n=10) were...
The aim of this study was to investigate the role of forebrain serotonin projections in behavioural models with relevance to schizophrenia. Mice received stereotaxic micro-injections of the serotonin neurotoxin 5,7-dihydroxytryptamine into the median raphe nucleus (MRN). Two weeks later, MRN-lesioned mice were hyperactive at baseline and showed enhanced locomotor hyperactivity induced by...
We have recently shown that sub-chronic phencyclidine (PCP) treatment produces social behaviour deficits in female rats which are reversed by ziprasidone but not haloperidol or clozapine. This investigation was designed to extend the previous findings and identify the role of 5-HT(1A) receptors in mediating the effects of these drugs in this model. Female hooded-Lister rats received vehicle...
Misuse of anabolic-androgenic steroids (AASs) is increasing, and appears to have much in common with the use of substances known to induce drug dependence. Moreover, persons who abuse AASs also tend to abuse other psychotropic drugs such as amphetamine or 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The aim of this study was to investigate whether nandrolone (5 x 5 or 5 x 20 mg/kg)...
Using the elevated plus-maze (EPM), Wistar rats can be distinguished into high (HA) or low anxiety (LA) subjects. These differences seem to reflect traits, since HA and LA rats vary also in other anxiety-dependent tasks, neurochemical mechanisms, and psychopharmacological reactivity, including lasting consequences after single treatment with 3,4-methylenedioxymethamphetamine (MDMA). Here, we...
Sub-chronic phencyclidine (PCP) treatment mimics certain aspects of schizophrenia symptomology in rats. However, there is a marked lack of attempts to model negative symptomology such as social behaviour deficits in female rats. This study was conducted to assess whether sub-chronic PCP treatment produces social interaction deficits in female rats and to ascertain if these deficits can be...
Anxiety was assessed in rats treated with 5mg/kg of PCP bid for 7 days. One week after withdrawal, measures were collected in the light/dark apparatus and during exposure to a cat odor. PCP decreased time spent in the lit area and number of contacts with a cat collar. PCP thus amplified rats' fear of unprotected environments and predatory threats, which seems compatible with the distorted...
Phencyclidine (PCP), an NMDA antagonist, has been shown to mimic some aspects of schizophrenia including positive, negative and cognitive symptoms. Previous studies in this laboratory have shown a selective reversal-learning deficit following acute PCP administration, a deficit that is attenuated by atypical, but not classical, antipsychotic treatment. However, acute PCP has limitations for...
The hypo-glutamatergic hypothesis of schizophrenia is not only based on the phencyclidine-(PCP)-induced psychosis in mentally healthy humans but also on studies with schizophrenic patients showing deficits in post mortem hippocampal N-methyl-d-aspartate (NMDA) receptor gene expression and deficits in prepulse inhibition. The inbred mouse strains CPB-K and BALB/cJ display considerable...
The expression of the alpha7-nicotinic acetylcholine receptor is diminished in selected brain areas of patients with schizophrenia. This diminished expression may account for the pathophysiological deficits of sensory inhibition and smooth pursuit eye movement performance in these patients. Furthermore, the deficits in sensory inhibition and smooth pursuit eye movement performance in...
Cannabinoid receptors have been implicated as having important roles in human cognitive processes, especially memory and attention. While some work has studied the effects of the active ingredient in marijuana, delta-9-tetrahydrocannabinol (THC), on short-term memory, no work has examined the involvement of these receptors in mediating attention. Therefore, the present study compared the...
The neural basis of ibogaine's effects on drug-related behaviours is unclear. One possibility is that ibogaine interferes with the shared capacity of many addictive agents to stimulate brain dopamine activity, but reports of ibogaine effects on dopamine activity have been inconsistent. Our study suggests such inconsistencies may result from variations in prior drug exposure. If ibogaine blocks...
Previous studies have shown that 2 h restraint stress induces deficits in open arm exploration of an elevated plus maze 24 h later. This effect was attenuated by a post-stress systemic injection of the 5-HT non-selective agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). To verify a possible involvement of hippocampal 5-HT1A receptors in this effect, rats were stereotaxically implanted with...
This study sought to investigate possible interactions between antidepressant agents and lysergic acid diethylamide (LSD) in humans through the use of retrospective questionnaires. Ten subjects were identified who used LSD during chronic (3 weeks or longer) periods of antidepressant administration. These subjects were asked to describe the phenomenological effects of self-administered...
Phencyclidine (PCP) produces a psychotic reaction in humans which closely resembles an acute episode of schizophrenia and has therefore been given an increasing amount of attention as a model for schizophrenia. The present article reviews the behavioral and neurochemical effects of PCP in both humans and animals. Where possible, comparisons are made between the effects of PCP and amphetamine....
3,4-Methylenedioxymethamphetamine (MDMA) is a phenethylamine with potent effects on serotonergic neurotransmission which has been the object of controversy over its potential as a therapeutic adjunct versus its possible risks for causing neurotoxic injury. This paper discusses the background, methodology and preliminary findings of the first FDA approved Phase I study prospectively evaluating...
We generated dose-response data for the endogenous and ultra-short-acting hallucinogen, N,N-dimethyltryptamine (DMT), in a cohort of experienced hallucinogen users, measuring multiple biological and psychological outcome measures. Subjective responses were quantified with a new rating scale, the HRS, which provided better resolution of dose effects than did the biological variables. A tolerance...
In the (re-)animated debate on consciousness we focus on three questions: Who has consciousness? What is its neuronal basis? What is its function? Regarding the first, we suggest that consciousness is exclusive to living organisms able to distinguish self from non-self. It may be restricted further to organisms who possess a repertoire of overt and covert behaviour which can be voluntarily...
Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by both norharman and ibogaine. In addition, norharman reduced also the withdrawal grooming and rearing. It is concluded...