RESUMO
We produced thiamine-deficient (TD) mice by TD diet treatment. The growth curve of mice on TD feeding was sharply increased until on the 10th day and subsequently the body weight gradually decreased. The mortality rate in mice was about 67% on the 30th day after the start of TD feeding. We performed the forced swimming test on the 10th and 20th day after the start of TD feeding. The duration of immobility in the forced swimming test was increased on the 20th day of TD feeding. Locomotor activity and motor co-ordination between the pair-fed control group and TD group on the 20th day of TD feeding were not significantly changed. Only a single injection of thiamine HCI (50 mg/kg, s.c.) on the 10th day after the start of a TD diet shortened the increased duration of immobility in the forced swimming test on the 20th day after the start of TD feeding. Whereas these reversal effects of thiamine treatment on the 20th day were not found when the treatment was given on the 19th day after the start of a TD diet. On the 20th day after the start of TD feeding, the increased duration of immobility time induced by TD was shortened by chronic administration of the tricyclic antidepressant imipramine (10 mg/kg, i.p.). These results suggested that behavioral changes in the forced swimming test might be involved in the degeneration of serotonergic and noradrenergic neurons.
Assuntos
Comportamento Animal/fisiologia , Depressão/psicologia , Deficiência de Tiamina/psicologia , Animais , Antidepressivos Tricíclicos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Depressão/tratamento farmacológico , Depressão/fisiopatologia , Dieta , Modelos Animais de Doenças , Imipramina/administração & dosagem , Imipramina/uso terapêutico , Injeções Intraperitoneais , Injeções Subcutâneas , Longevidade/efeitos dos fármacos , Longevidade/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Natação/fisiologia , Tiamina/administração & dosagem , Tiamina/uso terapêutico , Deficiência de Tiamina/tratamento farmacológico , Deficiência de Tiamina/fisiopatologia , Fatores de TempoRESUMO
We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and omega-conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of alpha1A, alpha1B, alpha1E, alpha1F, alpha1H, beta3, and beta4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and omega-conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.
Assuntos
Anlodipino/farmacologia , Analgésicos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Gânglios Espinais/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Dor/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Eletrofisiologia , Formaldeído/antagonistas & inibidores , Formaldeído/toxicidade , Injeções Espinhais , Camundongos , Neurônios Aferentes/fisiologia , Dor/induzido quimicamente , Reação em Cadeia da Polimerase , RNA/isolamento & purificação , Ratos , Ratos WistarRESUMO
Immunohistological study revealed the differential localization of subtypes of voltage-dependent calcium channels in the dorsal root ganglion neurons. Intrathecal injection of omega-conotoxin SVIB, an analogue of omega-conotoxin GVIA, which acts on N-type voltage-dependent calcium channels, significantly shortened the licking time in the late phase of a formalin test.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo N/análise , Gânglios Espinais/química , Neurônios/química , Nociceptores/efeitos dos fármacos , ômega-Conotoxinas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Canais de Cálcio Tipo N/fisiologia , Gânglios Espinais/citologia , Injeções Espinhais , Camundongos , Neurônios/efeitos dos fármacos , Medição da Dor/efeitos dos fármacosRESUMO
We investigated the antinociceptic effects of cilnidipine, a dihydropyridine derivative which acts on both L- and N-type voltage-dependent calcium channels, in mice. Intrathecally injected cilnidipine showed significant analgesic effect in formalin test. Cilnidipine significantly suppressed N-type currents in dorsal root ganglion (DRG) cells. Our findings apparently support the idea that cilnidipine attenuates synaptic neurotransmission by inhibiting N-type calcium channels in DRG neurons.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo N/metabolismo , Di-Hidropiridinas/farmacologia , Nociceptores/efeitos dos fármacos , Animais , Canais de Cálcio Tipo N/genética , Relação Dose-Resposta a Droga , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Expressão Gênica/fisiologia , Hibridização In Situ , Camundongos , Camundongos Endogâmicos C57BL , Nicardipino/farmacologia , RNA Mensageiro/análise , Transmissão Sináptica/efeitos dos fármacosRESUMO
The inhibitory effect of intracerebroventricularly-administered [D-Arg(2), beta-Ala(4)]-dermorphin (1-4) (TAPA), a highly selective mu(1)-opioid receptor agonist, on mouse gastrointestinal transit was compared with that of morphine and [D-Ala(2), N-methyl-Phe(4), Gly(5)-ol]-enkephalin (DAMGO). When administered intracerebroventricularly 5 min before the oral injection of charcoal meal, TAPA (10-100 pmol), morphine (0.25-4 nmol), and DAMGO (20-80 pmol) dose-dependently inhibited gastrointestinal transit of charcoal. The inhibitory effect of each mu-opioid receptor agonist was completely antagonized by naloxone, a nonselective opioid receptor antagonist. The inhibitory effects of morphine and DAMGO were significantly antagonized by both beta-funaltrexamine, a selective mu-opioid receptor antagonist, and naloxonazine, a selective mu(1)-opioid receptor antagonist. In contrast, the inhibitory effect of TAPA was not affected at all by beta-funaltrexamine, naloxonazine, nor-binaltorphimine (a selective kappa-opioid receptor antagonist), or naltrindole (a selective delta-opioid receptor antagonist). These results suggest that the inhibitory effect of TAPA on gastrointestinal transit may be mediated through an opioid receptor mechanism different from that of morphine and DAMGO.