Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

Background Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants. Results This study examined the effect of chronic administration of pseudoephedrine in rat nucleus accumbens and striatum and identified three further similarities to amphetamine. (i) Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii) In animals chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals indicating cross-tolerance for the two drugs. (iii)The known involvement of the dopamine system in the response to amphetamine and pseudoephedrine was further confirmed in this study by demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited [3H]dopamine uptake in synaptosomal preparations. Conclusion This work has demonstrated further similarities of the effect of pseudoephedrine to those of amphetamine in brain areas known to be associated with drug addiction. The most significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine. This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are required to establish whether despite its considerable lower potency, pseudoephedrine could pose health and addiction risks in humans similar to that of known psychostimulants

Okra (Abelmoschus esculentus Linn) inhibits lipopolysaccharide-induced inflammatory mediators in BV2 microglial cells

Purpose: To investigate the inhibitory effects of okra (Abelmoschus esculentus Linn.) extract on the production of reactive oxygen species (ROS) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV2 microglia.Methods: Okra was extracted with ethanol by Soxhlet extraction. Non-cytotoxic doses of okra at concentrations of 50, 100 and 200 μg/mL were used in this study. BV2 cells were cultured and treated with LPS in the presence or absence of okra at the concentrations indicated above. ROS, nitric oxide (NO), tumor necrotic factor alpha (TNF-α), interleukin 1 beta (IL-1β), phosphorylation levels of nuclear factor-kappa B (NF-kB) p65 and Akt were determined.Results: Treatment of BV2 cells with okra concentrations of 50, 100 and 200μg/mL significantly suppressed LPS-induced NO as well as ROS compared to untreated cells. There was also a significant decrease in the production of TNF-α and IL-1β in okra-treated BV2 microglia cells. The level of LPSinduced NF-kB p65 phosphorylation was significantly decreased by okra treatment. In addition, okra inhibited LPS-induced Akt phosphorylation, which is an upstream molecule of NF-kB.Conclusion: Okra exerts anti-oxidative and anti-inflammatory effects in LPS-stimulated BV2 microglial cells by suppressing Akt-mediated NF-κB pathway. This suggests that okra might be a valuable agent for the treatment of anti-neuroinflammatory diseases mediated by microglial cells.Keywords: Abelmoschus esculentus Linn, Inflammatory cytokines, Lipopolysaccharide, Neuroinflammation, Microglia, Reactive oxygen specie

Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

Background: Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants. Results: This study examined the effect of chronic administration of pseudoephedrine in rat nucleus accumbens and striatum and identified three further similarities to amphetamine. (i) Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii) In animals chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals indicating cross-tolerance for the two drugs. (iii)The known involvement of the dopamine system in the response to amphetamine and pseudoephedrine was further confirmed in this study by demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited [3H]dopamine uptake in synaptosomal preparations. Conclusion: This work has demonstrated further similarities of the effect of pseudoephedrine to those of amphetamine in brain areas known to be associated with drug addiction. The most significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine. This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are required to establish whether despite its considerable lower potency, pseudoephedrine could pose health and addiction risks in humans similar to that of known psychostimulants

Effects Of Amphetamine-Cns Depressant Combinations And Of Other Cns Stimulants In Four-Choice Drug Discriminations

Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine–pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs at these doses, and saline (methamphetamine–morphine group). After 10 to 13 months of training, the pigeons averaged more than 90% of their responses on the appropriate key during training sessions. In subsequent testing, dose-response curves were determined for the individual drugs, for a wide range of dose combinations of the training drugs, and for two drugs to which the pigeons had not been exposed previously (pseudoephedrine and nicotine). After low test doses of the training drugs, pigeons responded on the saline key. As the dose increased, responding on the key associated with that drug during training sessions increased. When training drugs were combined at doses that were not discriminable when given alone, responding occurred on the saline key. When a discriminable dose of one training drug was combined with a nondiscriminable dose of the other training drug, responding occurred on the key associated with the discriminable dose. When both drugs were given at discriminable doses, responding almost always occurred on the drug-combination key. The response-rate decreasing effects of pentobarbital and amphetamine were mutually antagonized when the drugs were combined, but the rate-decreasing effects of morphine and methamphetamine were not. After low doses of pseudoephedrine and nicotine, pigeons in both groups responded on the saline key. After higher doses of pseudoephedrine and nicotine, responding in the amphetamine–pentobarbital group occurred primarily on the amphetamine key. In the methamphetamine–morphine group, higher doses of pseudoephedrine and especially nicotine engendered more responding on the combination key than had occurred in the other group. The four-choice procedure can reveal subtle effects in the discrimination of individual drugs and drug combinations that are not apparent with procedures offering fewer response alternatives