European journal of pharmacology
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Comparative Study
Stressors affect the response of male and female rats to clomipramine in a model of behavioral despair (forced swim test).
Aim of the present study was to evaluate the effects of physical stressors (electric foot-shocks) on effect of the antidepressant drug, clomipramine and plasma corticosterone levels in male and female rats tested in a model of behavioral despair (forced swim test,). Male and female rats of the Wistar strain were injected with clomipramine (50 mg/kg, i.p.) or saline. A group of animals also received electric shocks of different intensity and duration of 24, 5 and 1 h before being subjected to forced swim test. ⋯ However, severe shocks were followed by a surge of plasma corticosterone levels in both male and female clomipramine-treated rats. These results demonstrate that duration and intensity of stressful stimuli may deeply affect the behavioral response of rats in forced swim test and influence clomipramine effect in this behavioral model depending on gender-based variables, probably of the hormonal type. Plasma corticosterone levels correlate with the behavioral response to clomipramine treatment suggesting that reactivity of hypothalamus-pituitary-adrenal axis to stress may be involved in the antidepressant effect of this drug.
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Comparative Study
CHF3381, a novel antinociceptive agent, attenuates capsaicin-induced pain in rats.
Here, we have examined the effect of the novel antinociceptive agent CHF3381 on the development of nocifensive behaviour as well as secondary mechanical allodynia and hyperalgesia induced by intraplantar injection of capsaicin in rats. Vehicle, CHF3381 or gabapentin were orally administered 1 h before capsaicin injection. The duration of nocifensive behaviour was measured during the first 5 min after capsaicin injection. ⋯ Gabapentin weakly inhibited the development of nocifensive behaviour and mechanical allodynia. On the contrary, gabapentin (100 mg/kg) completely prevented the development of mechanical hyperalgesia. In conclusion, CHF3381 had full efficacy for all the capsaicin-induced pain parameters tested, suggesting that CHF3381 may have a therapeutic utility in the management of pain states involving central sensitisation.
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Comparative Study
Anti-allodynic interactions between NMDA receptor channel blockers and morphine or clonidine in neuropathic rats.
Previous studies suggested that combining N-methyl-d-aspartate (NMDA) receptor antagonists with either mu-opioid agonist morphine or alpha2-adrenoreceptor agonist clonidine results in the significant synergistic enhancement of analgesic activity in the animal models of acute and neuropathic pain. When given alone, NMDA receptor antagonists, morphine and clonidine are capable of attenuating tactile allodynia associated with chronic nerve injury. The present study aimed to assess anti-allodynic effects of these compounds and to test additivity of these interactions using isobolographic analysis. ⋯ None of the tested combinations produced supra-additive, synergistic effects. In fact, memantine+clonidine, neramexane+clonidine and morphine+neramexane were producing simple additive effects, while morphine+memantine was characterized as the infra-additive combination. Thus, despite expectations based on previous studies, NMDA receptor channel blockers, memantine and neramexane, produce no synergistic interactions with either morphine or clonidine when administered acutely to rats with nerve injury-induced tactile allodynia.