Morphine-mediated AC activation requires Src kinase, which was postulated to be responsible for morphine tolerance and dependence. Currently, we demonstrated that following long-term morphine treatment and subsequent naloxone precipitation, microglia was activated, which appeared to be obligatory for CD44 expression and production of IL-1beta, iNOS, MCP-1, MIP-1alpha, MIP-1beta, and TNF-alpha. ...

The effects of ondansetron, a highly potent and selective 5-HT3 receptor antagonist, in the prevention of tolerance to and dependence on morphine were studied in mice using a 9-day schedule. Chronic administration of morphine (10 mg/kg i.p. twice daily for 9 days) produced tolerance to the analgesic effects and animals showed withdrawal jumps on day 10 when challenged with naloxone (2 mg/kg). C...

Opiate dependence and withdrawal have long been hypothesized to enhance the reinforcing effects of opiates; however, opiate agonist self-administration in these states has yet to be systematically assessed. To address this issue, the reinforcing property of the short-acting mu-opioid agonist, remifentanil, was assessed in morphine-dependent (MD), morphine-dependent and -withdrawn (MW), and nond...

Background: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in transient receptor potential vanilloid type 1 (TRPV-1) expression during admi...

BACKGROUND Morphine induces adaptive changes in gene expression throughout the reward circuitry of the brain. Here, we investigated the acute and chronic effects of morphine on mRNA levels of κ-opioid receptor in the rat mesocorticolimbic system. METHODS Three groups of rats received ip injection of saline, acute morphine (8.0 mg/kg) and repeated morphine (8.0 mg/kg, once daily for 5 consecut...

BACKGROUND Clinical observation and experimental studies have indicated that a single exposure to morphine could induce tolerance and dependence. It has become a concern in clinical antinociceptive practice. However, the underling mechanism remains unknown. This study was designed to explore the changes of dopamine (DA) neuron activities in the ventral tegmental area (VTA) by employing a spectr...

Single morphine injections induce a state of acute opioid dependence measured by an increase in naloxone potency to precipitate withdrawal. Repeated morphine exposure (daily/weekly intervals) results in further potentiation of naloxone potency, perhaps due to conditioning mechanisms. The current study tested the hypothesis that previously neutral stimuli could elicit a conditioned potentiation ...

Objective(s) Single injection of naloxone, a selective antagonist of morphine, prior to the drug conditioning testing was used to investigate on morphine dependence. Materials and Methods Conditioning to morphine (2.5-10 mg/kg, s.c.) was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Nitric oxide agents were microinjected into the central amygdala prior ...

Combined use of an opioid with a psychostimulant is popular among drug abusers. Such “polydrug use” may increase drug effects or attenuate adverse effects of either drug alone. We proposed that a combination of methamphetamine (meth) and morphine may change physical opioid withdrawal symptoms. Adult male rats were chronically injected with cumulative subcutaneous (s.c.) doses of morphine, meth ...

      The effect of aqueous extract of Nepata glomerulosa Boiss. aerial parts on morphine withdrawal syndrome was investigated in mice. Dependence was induced by subcutaneous injections of morphine for 3 consecutive days. On day 4, morphine was injected 2 h prior to intraperitoneal injection of naloxone. The number of jumps during a 20 min. period after naloxone injection was considere...