4-Bromo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25B-NBOMe) is a hallucinogen exhibiting high binding affinity for 5-HT serotonin receptors. In the present work, we investigated its effect on dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. Hallucinogenic activity, impact on cognitive and motor functions, and anxiogenic/anxiolytic properties of this compound were also tested.
View Article and Find Full Text PDFRationale: According to psychological theories, cognitive distortions play a pivotal role in the aetiology and recurrence of mood disorders. Although clinical evidence for the coexistence of depression and altered sensitivity to performance feedback is relatively coherent, we still do not know whether increased or decreased sensitivity to positive or negative feedback is associated with 'pro-depressive' profile in healthy subjects.
Objective: Our research has been designed to answer this question, and here, we present the first steps in that direction.
Acknowledgments: This study was supported by the Grant No 2013/09/B/NZ7/04104 from the National Science Center (Poland).
View Article and Find Full Text PDFPurpose: Tryptamine hallucinogen 5-methoxy--diisopropyltryptamine (5-MeO-DIPT) is a serotonin transporter inhibitor with high affinity for serotonin 5-HT and 5-HT receptors. We showed previously that 5-MeO-DIPT in a single dose increased neurotransmitter release in brain regions of rats and elicited single- and double-strand DNA breaks. Herein we investigated the effects of repeated-intermittent 5-MeO-DIPT administration in adolescence on dopamine (DA), serotonin (5-HT) and glutamate release in brain regions of adult rats.
View Article and Find Full Text PDFNeurosci Biobehav Rev
December 2018
Depressive disorder accounts for a substantial proportion of psychiatric problems across the globe and has a devastating impact on quality of life and occupational function. Psychological models of depression emphasize the causal role of cognitive distortions in this disease, and cognitive problems have been included in the diagnostic criteria for depressive episodes. Here, we focus on recent progress in preclinical modelling of aberrations in one of the most important neurocognitive mechanisms involved in the manifestation of depression - abnormal sensitivity to positive and negative feedback.
View Article and Find Full Text PDFBackground: Preclinical and clinical studies have suggested a beneficial effect of combination treatment with atypical antipsychotic drugs and antidepressants (ADs) in schizophrenia and in drug-resistant depression.
Methods: In the present study, we investigated the effect of chronic administration of risperidone and ADs (escitalopram or mirtazapine), given separately or jointly on the extracellular levels of dopamine (DA) and serotonin (5-HT) in the rat frontal cortex. The animals were administered risperidone (0.
Background: According to the European Drug Report, the use of novel psychoactive substances (NPS) is constantly growing. NPS are widely abused by human adolescent subjects. 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is one of the most frequently used hallucinogenic NPS.
View Article and Find Full Text PDFAccording to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft.
View Article and Find Full Text PDFBackground: Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms often accompanied by depression and cognitive deficits. Positive symptoms, like delusions and hallucinations are caused by an excess of dopamine (DA) signaling and are treated with the second generation antipsychotic drugs. Negative symptoms of schizophrenia are represented by social withdrawal, apathy and blunted emotional response.
View Article and Find Full Text PDFLSP4-2022 is a novel, orthosteric agonist of mGlu receptor that induces antipsychotic-like activity in animal studies. In the present study, the involvement of 5-HT receptors in LSP4-2022-induced antipsychotic actions and the neurochemical background of that interaction were investigated. In several behavioral tests the actions of effective doses of the compound (0.
View Article and Find Full Text PDF5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors.
View Article and Find Full Text PDFOur previous study showed that dietary zinc restriction induces depression-like behavior with concomitant up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Because metal ions, oxidative stress, and inflammation are involved in depression/NMDAR function, in the present study, bio-elements (zinc, copper, iron, magnesium, and calcium), oxidative (thiobarbituric acid-reactive substances; protein carbonyl content), and inflammatory (IL-1α, IL-1β) factors were measured in serum, hippocampus (Hp), and prefrontal cortex (PFC) of male Sprague-Dawley rats subjected to a zinc-adequate (ZnA) (50 mg Zn/kg) or a zinc-deficient (ZnD) (3 mg Zn/kg) diet for 4 or 6 weeks. Both periods of dietary zinc restriction reduced serum zinc and increased serum iron levels.
View Article and Find Full Text PDFNew psychoactive "designer drugs" are synthetic compounds developed to provide similar effects to illicit drugs of abuse, but not subjected to legal control. The rapidly changing legal status of novel psychoactive drugs triggers the development of new compounds, analogs of well-known amphetamine or mescaline. New designer drugs used as substitutes in ecstasy pills are the least investigated and can cause life-threatening effects on users.
View Article and Find Full Text PDFRationale: Diverse preclinical studies suggest the potential therapeutic utility of the modulation of the glutamatergic system in brain via metabotropic glutamate (mGlu) receptors. Lu AF21934, a positive allosteric modulator of the mGlu4 receptor, was previously shown to reverse behavioral phenotypes in animal models thought to mimic positive, negative, and cognitive symptoms of schizophrenia.
Objectives: To begin elucidating the brain circuitry involved in mGlu4 receptor pharmacology and add mechanistic support to Lu AF21934-induced phenotypic responses, the potential involvement of 5-HT1A receptors in these antipsychotic-like effects was explored.
Background: The psychostimulant 3,4-methylenedioxymethamphetamine (MDMA) with a strong addictive potential is widely used as a recreational drug. Neurotoxicity of MDMA is related with the generation of highly reactive free radicals.
Methods: MDMA was given in doses of 20 and 40mg/kg ip alone or in combination with caffeine (CAF) 10mg/kg ip.
Background: Inflammation-induced microglia activation and increased oxidative stress have been observed in neurodegenerative disorders, such as Parkinson's disease. The aim of our study was to determine the appropriate dose and route of LPS administration to study hydroxyl radical generation and extracellular level of dopamine (DA), glutamate (GLU) and adenosine (ADN) in the rat striatum as markers of DA neuron damage and glial cell activation. The effect of LPS administration on DA, DOPAC, HVA and hydroxyl radical tissue level was also examined.
View Article and Find Full Text PDFThe study shows effects of the nonselective adenosine A1/A2A receptor antagonist caffeine and the selective A2A receptor antagonist KW6002 on LPS-induced changes in the extracellular levels of dopamine (DA), glutamate, adenosine, hydroxyl radical, and A2A receptor density in the rat striatum. Intrastriatal LPS (10 μg) injection decreased extracellular level of DA and increased the level of adenosine, glutamate, and hydroxyl radical on the ipsilateral side 24 h after LPS administration. Caffeine (10 and 20 mg/kg i.
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