Cortical [alpha]1-adrenergic regulation of acute and sensitized morphine locomotor effects
ABSTRACT The role of α1-adrenergic transmission was tested on locomotor effects of acute or repeated morphine (5 mg/kg, i.p.) administration. Prazosin, an α1-adrenergic antagonist, administered 30 min before morphine, either systemically (0.5 mg/kg, i.p.) or locally and bilaterally into the prefrontal cortex (200 pmol/side) reduced the stimulatory influence of morphine on locomotion. The progressive increase of the locomotor response induced by repeated morphine injections was blocked by a prazosin pretreatment but not the behavioral sensitization on the test day. These data suggest that blockade of cortical α1-adrenergic receptors reduces the expression of acute and sensitized locomotor responses to morphine, but does not prevent the induction of behavioral sensitization.
Article: Effect of fluoxetine on tolerance to the analgesic effect of morphine in mice with skin cancer.[show abstract] [hide abstract]
ABSTRACT: Adjuvant drugs that attenuate or inhibit the development of tolerance to morphine may lead to improved management of pain in chronic diseases such as cancer. The aim of this study was to investigate effect of fluoxetine, a specific 5-HT (5-hydroxytryptamine, serotonin) reuptake inhibitor, on tolerance induced to the analgesic effect of morphine in mice with skin cancer. The study was carried out on female Swiss albino mice. For skin tumorigensis, mice were initiated with a single dose of 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by multiple doses of croton oil. Tolerance to morphine analgesia was induced by daily subcutaneous (sc) injections of morphine (5 mg/kg for 30 days) and assayed using the hot plate method. Results obtained from this study showed that pain thresholds in mice with skin cancer were significantly lower. Tolerance to the analgesic effect of morphine (5 mg/kg, sc) appeared at day 15, whereas in normal and skin tumor bearing mice co-treated daily with morphine (5 mg/kg, sc) and three different intraperitoneal (ip) doses of fluoxetine (0.16, 0.32 and 0.64 mg/kg) tolerance was observed at days 20, 25 and 30, respectively. In conclusion, our data indicate that concurrent use of morphine with fluoxetine may produce good cancer pain control and attenuate the development of tolerance.Pharmacological reports: PR 61(3):453-8. · 2.44 Impact Factor