Possible Potentiating Effects of Combined Administration of Alcohol, Caffeine, and Nicotine on In Vivo Dopamine Release in Addiction-Related Circuits Within the CNS of Rats.

Background: Studies that assess the effects of the interaction of psychoactive substances on dopamine release, the key neurotransmitter in the neurochemical and behavioral effects related to drug consumption, are crucial to understand both their roles and the dysfunctions they produce in the central nervous system.

Objective: We evaluated the effects of individual and combined administration of the three most widely consumed psychoactive substances in the world, ethanol, caffeine, and nicotine, on dopaminergic neurotransmission in three brain regions of rats related to addiction: the prefrontal cortex (PFC), the nucleus accumbens (NAcc), and the dorsal striatum.

Methods: The dopamine levels were measured in vivo by cerebral microdialysis associated with HPLC-ED.

Role of voltage-dependent calcium channels on the striatal in vivo dopamine release induced by the organophosphorus pesticide glyphosate.

In the present study, we investigated the role of voltage-sensitive calcium channels (VSCCs) on the striatal dopamine release induced by the pesticide glyphosate (GLY) using selective VSCC inhibitors. The dopamine levels were measured by in vivo cerebral microdialysis coupled to HPLC-ED. Nicardipine (L-type VSCC antagonist) or ω-conotoxin MVIIC (non-selective P/Q-type antagonist) had no effect on dopamine release induced by 5 mM GLY.

Role of voltage-sensitive Ca channels in the in vivo dopamine release induced by the organophosphorus pesticide glufosinate ammonium in rat striatum.

The possible role of voltage-sensitive calcium channels (VSCC) activation in the glufosinate ammonium (GLA)-induced dopamine release was investigated using selective VSCC blockers and the dopamine levels were measured by HPLC from samples obtained by in vivo cerebral microdialysis. While pretreatment with 10 μM flunarizine (T-type VSCC antagonist) or nicardipine (L-type VSCC antagonist) had no statistically significant effect on dopamine release induced by 10 mM GLA, pretreatment with 100 μM of both antagonists, or 20 μM ω-conotoxin MVIIC (non-selective P/Q-type VSCC antagonist) significantly decreased the GLA-induced dopamine release over 72.2%, 73%, and 70.

Toxic Effects of Glyphosate on the Nervous System: A Systematic Review.

Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans.

Systematic Review of Calcium Channels and Intracellular Calcium Signaling: Relevance to Pesticide Neurotoxicity.

Pesticides of different chemical classes exert their toxic effects on the nervous system by acting on the different regulatory mechanisms of calcium (Ca) homeostasis. Pesticides have been shown to alter Ca homeostasis, mainly by increasing its intracellular concentration above physiological levels. The pesticide-induced Ca overload occurs through two main mechanisms: the entry of Ca from the extracellular medium through the different types of Ca channels present in the plasma membrane or its release into the cytoplasm from intracellular stocks, mainly from the endoplasmic reticulum.

Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?-A Systematic Review.

Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these insecticides is due to this mechanism of action, since they act as potent agonists of insect nAChRs, presenting low affinity for vertebrate nAChRs, which reduces potential toxic risk and increases safety for non-target species. However, although neonicotinoids are considered safe, their presence in the environment could increase the risk of exposure and toxicity.

Participation of glutamatergic and nitrergic systems in the striatal dopamine release induced by isatin, a MAO inhibitor.

Isatin is a biofactor with different biochemical and pharmacological properties whose effects attract much attention because it is an endogenous inhibitor of the monoamine oxidase in the brain. When exogenously administrated, isatin increases dopamine levels in intact and denervated striatum of rats, an effect that could indicate its potential as a therapeutic agent in Parkinson disease. However, the neurochemical mechanisms by which isatin increases dopamine in the striatum are poorly understood.

Do Naturally Occurring Antioxidants Protect Against Neurodegeneration of the Dopaminergic System? A Systematic Revision in Animal Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by a significant decrease in dopamine levels, caused by progressive degeneration of the dopaminergic neurons in the nigrostriatal pathway. Multiple mechanisms have been implicated in its pathogenesis, including oxidative stress, neuroinflammation, protein aggregation, mitochondrial dysfunction, insufficient support for neurotrophic factors and cell apoptosis. The absence of treatments capable of slowing or stopping the progression of PD has increased the interest in the natural antioxidant substances present in the diet, since they have multiple beneficial properties and it is possible that they can influence the mechanisms responsible for the dysfunction and death of dopaminergic neurons.

Possible synergies between isatin, an endogenous MAO inhibitor, and antiparkinsonian agents on the dopamine release from striatum of freely moving rats.

Isatin is an endogenous indole that inhibits monoamine oxidase (MAO). When exogenously administered, it increases the striatal dopamine and acetylcholine levels and presents neuroprotective effects in the brain. Previous studies show that intrastriatal administration of isatin increased the in vivo dopamine release from striatum in a concentration-dependent form.

Clothianidin, a neonicotinoid insecticide, activates α4β2, α7 and muscarinic receptors to induce in vivo dopamine release from rat striatum.

Clothianidin (CLO) is a neonicotinoid insecticide that produces toxic effects in experimental animals and humans. These effects are associated primarily to its action as a nicotinic agonist, acting on insect and vertebrate nicotinic acetylcholine receptors (nAChRs), but little is known about the mechanisms of action on the mammalian nervous system. In the rat striatum, CLO induces increases in the dopamine overflow in a concentration-dependent manner.

Mechanisms of action of paraoxon, an organophosphorus pesticide, on in vivo dopamine release in conscious and freely moving rats.

Paraoxon is the active metabolite of parathion, an organophosphorus pesticide which can cause neurotoxic effects in animals and humans. In the present work, we investigated the effects of 5 mM paraoxon on striatal dopamine, DOPAC and HVA levels in conscious and freely moving rats, after treatment with TTX, reserpine, nomifensine, KCl, Ca-free/EDTA medium, AP-5 or L-NAME. The intrastriatal administration of paraoxon for 60 min, through the microdialysis probe, significantly produced an increase of the dopamine to 1066 ± 120%, relative to basal levels.

Characterization of acute intrastriatal effects of paraoxon on in vivo dopaminergic neurotransmission using microdialysis in freely moving rats.

Paraoxon (POX) is an extremely neurotoxic organophosphorous compound (OP) which main toxic mechanism is the irreversible inhibition of cholinesterase. Although the cholinergic system has always been linked as responsible for its acute effects, experimental studies have suggested that the dopaminergic system also may be a potential target for OPs. Based on this, in this study, the acute intrastriatal effects of POX on dopaminergic neurotransmission were characterized in vivo using brain microdialysis in freely moving rats.

Effects of Caffeine on Behavioural and Cognitive Deficits in Rats.

There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments.

Role of voltage-gated calcium channels on striatal dopamine release induced by inorganic mercury in freely moving rats.

The possible role of voltage-sensitive calcium channels (VSCC) activation on the HgCl-induced dopamine release was investigated using selective VSCC blockers and the dopamine levels were measured by HPLC from samples obtained by in vivo brain microdialysis. Infusion of HgCl in nicardipine (10 or 100 μM) or flunaricine (10 μM) pretreated animals had no significant effect on dopamine release induced by HgCl. Pretreatment with 100 μM flunaricine, 20 μM ω-conotoxin MVIIC, or ω-conotoxin GVIA significantly decreased the HgCl-induced dopamine release over 61%, 88%, and 99%, respectively.

Hippocampal and cerebellar histological changes and their behavioural repercussions caused by brain ischaemic hypoxia experimentally induced by sodium nitrite.

Introduction: Brain ischaemic hypoxia can produce severe neurological damage that leads to behavioural disorders. This research analysed the hippocampal and cerebellar histological alterations caused by brain ischaemic hypoxia experimentally induced by sodium nitrite (NaNO) and possible direct repercussions of this hypoxia on behaviour.

Methodology: An experimental study was carried out by administering 60mg/kg NaNO to 10 Wistar rats at 3 months of age for 15 consecutive days.

Effects and mechanism of action of isatin, a MAO inhibitor, on in vivo striatal dopamine release.

Isatin is an endogenous indole that inhibits monoamine oxidase (MAO), being more selective for MAO-B than MAO-A isoform. By inhibiting MAO, isatin increases dopamine levels in the brain and, in animal models of Parkinson's disease (PD) isatin is able to prevent dopamine depletion. Contradictorily, some studies indicate that isatin did not increase striatal dopamine levels, although it was able to improve the motor signs in PD model.

Role of glutamate receptors and nitric oxide on the effects of glufosinate ammonium, an organophosphate pesticide, on in vivo dopamine release in rat striatum.

The purpose of the present work was to assess the possible role of glutamatergic receptors and nitric oxide (NO) production on effects of glufosinate ammonium (GLA), an organophosphate pesticide structurally related to glutamate, on in vivo striatal dopamine release in awake and freely moving rats. For this, we used antagonists of NMDA (MK-801 and AP5) or AMPA/kainate (CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (l-NAME and 7-NI), to study the effects of GLA on release of dopamine from rat striatum. So, intrastriatal infusion of 10mM GLA significantly increased dopamine levels (1035±140%, compared with basal levels) and administration of GLA to MK-801 (250μM) or AP5 (650μM) pretreated animals, produced increases in dopamine overflow that were ∼40% and ∼90% smaller than those observed in animals not pretreated with MK-801 or AP5.

Role of ionotropic glutamatergic receptors and nitric oxide in the effects of flutriafol, a triazole fungicide, on the in vivo striatal dopamine release.

Flutriafol is a triazole fungicide that induces spontaneous and depolarization-stimulated release of dopamine from rat striatum, although the neurochemical mechanism by which this fungicide induces this effect is unknown. The purpose of the present work was to assess the implication of ionotropic glutamatergic receptors and nitric oxide (NO) production in the flutriafol-induced dopamine release from rat striatum. To this, we have used non-competitive antagonists of NMDA (dizocilpine, MK-801), and (AMPA)/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX) receptors, or nitric oxide synthase (NOS) inhibitors (Nomega-nitro-L-arginine -L-NARG - and 7-nitro-indazol - 7-NI), to study the striatal dopamine release induced by flutriafol.

Hippocampal neuronal loss, decreased GFAP immunoreactivity and cognitive impairment following experimental intoxication of rats with aluminum citrate.

Aluminum (Al) is a neurotoxic agent with deleterious actions on cognitive processes. Nevertheless, few studies have investigated the neuropathological effects underlying the Al-induced cognitive impairment. We have explored the effects of acute Al citrate intoxication on both hippocampal morphology and mnemonic processes in rodents.

Effects of the neonicotinoids thiametoxam and clothianidin on in vivo dopamine release in rat striatum.

Thiamethoxam (TMX) and clothianidin (CLO) are neonicotinoids insecticides. The main characteristic of these pesticides is their agonist action on nicotinic acetylcholine receptors (nAChRs). In the present work it was studied and characterized the effects of TMX and CLO, in different concentrations, on dopaminergic system of rat striatum using in vivo brain microdialysis coupled to HPLC-EC.

Comparative effects of pesticides on in vivo dopamine release in freely moving rats.

The effects of different types of pesticides on the in vivo striatal dopamine release were investigated by using in vivo brain microdialysis technique. MPTP, paraquat, maneb, dicofol, DDT, lindane and flutriafol (1 mM) were administered directly into the striatum, and levels of dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovallinic acid (HVA) were measured using HPLC-EC. Intrastriatal administration of pesticides induced the following maximal effects on the dopamine levels: maneb 791 +/- 87%, dicofol 101 +/- 1%, DDT 779 +/- 32%, paraquat 956 +/- 80%, lindane 281 +/- 28% and flutriafol 218 +/- 51% with respect to basal levels.

Differential changes of neuroactive amino acids in samples obtained from discrete rat brain regions after systemic administration of saxitoxin.

Aspartic acid, glutamic acid, gamma-amino-n-butyric acid (GABA) and 2-aminoethanesulfonic acid are neuroactive amino acids. They are found in the central rat nervous system. Here, we have studied if a relationship exists between the presence of saxitoxin (STX) a paralytic poisoning shellfish (PSP) and the neuroactive amino acids.

Involvement of nicotinic and muscarinic acetylcholine receptors on striatal HgCl2-induced dopamine release in freely moving rats.

The possible role of acetylcholine receptors on the HgCl(2)-induced dopamine (DA) release from rat striatum was investigated by using in vivo brain microdialysis technique after administration of selective nicotinic and muscarinic receptor antagonists, mecamylamine and atropine, respectively. Intrastriatal infusion of 1mM HgCl(2) increased striatal DA to 1717.2+/-375.

Mediation of glutamatergic receptors and nitric oxide on striatal dopamine release evoked by anatoxin-a. An in vivo microdialysis study.

In this work, the involvement of ionotropic glutamatergic receptors and nitric oxide on striatal dopamine release induced by anatoxin-a was investigated in conscious and freely-moving rats. To study the participation of glutamatergic receptors, the effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and d(-)-2-amino-5-phosphonopentanoic acid (APV), were examined. The perfusion of 3.