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1.
Pharmacol Biochem Behav ; 207: 173222, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34197845

RESUMO

RATIONALE: Despite a long history of use in synaptic physiology, the lobster has been a neglected model for behavioral pharmacology. A restaurateur proposed that exposing lobster to cannabis smoke reduces anxiety and pain during the cooking process. It is unknown if lobster gill respiration in air would result in significant Δ9-tetrahydrocannabinol (THC) uptake and whether this would have any detectable behavioral effects. OBJECTIVE: The primary goal was to determine tissue THC levels in the lobster after exposure to THC vapor. Secondary goals were to determine if THC vapor altered locomotor behavior or nociception. METHODS: Tissue samples were collected (including muscle, brain and hemolymph) from Homarus americanus (N = 3 per group) following 30 or 60 min of exposure to vapor generated by an e-cigarette device using THC (100 mg/mL in a propylene glycol vehicle). Separate experiments assessed locomotor behavior and hot water nociceptive responses following THC vapor exposure. RESULTS: THC vapor produced duration-related THC levels in all tissues examined. Locomotor activity was decreased (distance, speed, time-mobile) by 30 min inhalation of THC. Lobsters exhibit a temperature-dependent withdrawal response to immersion of tail, antennae or claws in warm water; this is novel evidence of thermal nociception for this species. THC exposure for 60 min had only marginal effect on nociception under the conditions assessed. CONCLUSIONS: Vapor exposure of lobsters, using an e-cigarette based model, produces dose-dependent THC levels in all tissues and reduces locomotor activity. Hot water nociception was temperature dependent, but only minimal anti-nociceptive effect of THC exposure was confirmed.


Assuntos
Dronabinol/farmacologia , Vapor do Cigarro Eletrônico/farmacologia , Locomoção/efeitos dos fármacos , Nephropidae , Nociceptividade/efeitos dos fármacos , Administração por Inalação , Animais , Culinária/métodos , Dronabinol/administração & dosagem , Dronabinol/análise , Vapor do Cigarro Eletrônico/administração & dosagem , Sistemas Eletrônicos de Liberação de Nicotina , Feminino , Temperatura Alta , Maine , Masculino , Fumar Maconha/metabolismo , Dor/tratamento farmacológico , Ratos
2.
Toxicol Sci ; 168(1): 61-69, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30395337

RESUMO

Deltamethrin (DLM) is a commonly used pesticide that helps to control crop destruction, disease, and nuisance insects. In rodents DLM can produce choreoathetosis, salivation, and decreased acoustic startle responses (ASR). Herein, adult Sprague Dawley rats were assessed for ASR 2 h after DLM delivered in 5 ml/kg corn oil, however no decrease was observed. Therefore, a test-retest protocol was used to reduce variability, and the effects on ASR on postnatal day 15 (P15) and adult rats were assessed 2, 4, 6, and 8 h after DLM administration (0, 1, 2, or 4 mg/kg for P15 rats and 0, 2, 8, or 25 mg/kg for adults). In a separate set of rats identically treated, DLM levels were determined in blood and brain. DLM (8 or 25 mg/kg) in adult rats decreased ASR up to 4 h, whereas in P15 rats decreases were observed between 2 and 8 h. The adult 25 mg/kg group showed consistent signs of salivation and tremor, whereas in P15 rats salivation was observed in the 2 and 4 mg/kg groups and tremor was observed at all doses over the 8-h period. Mortality was observed in all P15 dose groups but not in adults. Dose-dependent increases of DLM in blood and brain regardless of age were observed. At approximately equivalent whole brain concentrations, effects were more pronounced in P15 rats than in adult rats. Comparable brain levels of DLM do not explain differences in ASR and tremor between the P15 and adult rats. These data indicate age-dependent differences in sensitivity to DLM.


Assuntos
Inseticidas/toxicidade , Nitrilas/farmacologia , Nitrilas/toxicidade , Piretrinas/farmacologia , Piretrinas/toxicidade , Reflexo de Sobressalto/efeitos dos fármacos , Estimulação Acústica , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Inseticidas/sangue , Inseticidas/farmacocinética , Masculino , Nitrilas/sangue , Piretrinas/sangue , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Salivação/efeitos dos fármacos , Tremor/induzido quimicamente , Tremor/metabolismo
3.
Toxicol Sci ; 165(2): 361-371, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29893952

RESUMO

Permethrin is a type I (noncyano) pyrethroid that induces tremors at high concentrations and increases acoustic startle responses (ASRs) in adult rodents, however its effects in young rats have been investigated to a limited extent. ASR and tremor were assessed in adult and postnatal day (P)15 Sprague-Dawley rats at oral doses of 60, 90, or 120 mg/kg over an 8 h period. Permethrin increased ASR in adults, regardless of dose, and 20% of the high-dose rats showed tremor at later time points. For the P15 rats all doses induced tremor at all time points, and ASR was increased at 2 h in the 90 and 120 mg/kg groups with a trend in the 60 mg/kg group compared with controls. The 60 mg/kg group showed increased ASR at 4 and 6 h, whereas the 90 mg/kg group showed no differences from the controls at these times. The 120 mg/kg group showed decreased ASR from 4- to 8-h posttreatment. P15 and adult rats both showed plasma and brain cis- and trans-permethrin increases after dosing. After the same dose of permethrin, P15 rats had greater cis- and trans-permethrin in brain and plasma compared with adults. P15 rats had an increased tremor response compared with adults even at comparable brain permethrin concentrations. For ASR, P15 rats responded sooner and showed a biphasic pattern ranging from increased to decreased response as a function of dose and time, unlike adults that only showed increases. Overall, young rats showed greater effects from permethrin compared with adults.


Assuntos
Encéfalo/efeitos dos fármacos , Inseticidas/toxicidade , Permetrina/toxicidade , Reflexo de Sobressalto/efeitos dos fármacos , Estimulação Acústica , Fatores Etários , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Feminino , Inseticidas/sangue , Inseticidas/química , Masculino , Permetrina/sangue , Permetrina/química , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Estereoisomerismo
4.
Int J Dev Neurosci ; 61: 92-111, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28655626

RESUMO

Most antidepressants inhibit monoamine reuptake. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) act on the 5-HT transporter (SERT) whereas norepinephrine-dopamine reuptake inhibitors (NDRIs) act on the norepinephrine and dopamine transporters. Epidemiological reports link SSRI use during pregnancy to an increased prevalence of autism spectrum disorder (ASD). We previously showed that perinatal exposure to the SSRI citalopram (CIT) results in rodent offspring that exhibit a number of behaviors consistent with an ASD-like phenotype. The present study examined the effect of perinatal exposure to CIT (at a lower dose), another SSRI, fluoxetine (FLX), and an NDRI, bupropion (BUP). Gravid Sprague-Dawley rats were subcutaneously injected twice per day (6h apart) with 5mg/kg CIT, 5mg/kg FLX, 15mg/kg BUP, or saline (SAL) from embryonic day (E) 6-21, and directly to the pups from postnatal day (P) 1-20. As adults, one male/female from each litter was given one of a series of tests. Both SSRI-exposed groups showed spatial learning deficits in Morris and radial water mazes, increased marble burying, increased acoustic startle, hypoactivity, and attenuated activity to the stimulating effect of the NMDA-R antagonist MK-801. The BUP-exposed group showed a reduction in elevated zero-maze quadrant entries and increased stimulated open-field activity following (+)-amphetamine challenge. These results reinforce concern about the use of antidepressants during pregnancy and highlight how the two classes of drugs produce different constellations of effects with more effects associated with the SSRIs. Further investigation into how antidepressants alter brain development leading to enduring adverse neurobehavioral effects is warranted.


Assuntos
Antidepressivos/toxicidade , Ansiedade/etiologia , Comportamento Exploratório/fisiologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reflexo de Sobressalto/fisiologia , Estimulação Acústica , Fatores Etários , Animais , Peso Corporal/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Relação Dose-Resposta a Droga , Antagonistas de Aminoácidos Excitatórios/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Feminino , Aprendizagem/efeitos dos fármacos , Aprendizagem/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Memória/fisiologia , Gravidez , Ratos , Ratos Sprague-Dawley , Reflexo de Sobressalto/efeitos dos fármacos , Comportamento Social
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