OBJECTIVES: Using the pentylenetetrazol (PTZ) discrimination assay, this study aims to investigate the effects of MG in responding to the PTZ stimulus and to assess the generalisation effects of withdrawal from MG to the PTZ stimulus.
METHODS: Rats (n = 20) were trained on a tandem (FR-10, VI-15) schedule of food reinforcement to press one lever after administration of the anxiogenic compound PTZ (16 mg/kg, i.p.) and an alternate lever after vehicle. Following acute tests, training was suspended, and rats were chronically treated with MG or morphine at 8-h intervals for 9 days and withdrawal was precipitated on the tenth day using naloxone (1 mg/kg, i.p.). The rats were tested for generalisation to PTZ at 2, 8 and 24 h after the last dose of MG or morphine administration.
RESULTS: Unlike morphine that produced dose-related PTZ-like stimulus, MG at 3, 10, 30 and 45 mg/kg doses showed no substitution to the PTZ discriminative stimulus. In contrast to morphine which produced a time-dependent generalisation to the PTZ stimulus, naloxone did not precipitate withdrawal effects in MG-treated rats as they selected the vehicle lever at three withdrawal time points.
CONCLUSION: These results demonstrate that MG produces a very different response to morphine withdrawal that is not associated with anxiogenic-like subjective symptoms. These characteristics of MG may provide further support for use as a novel pharmacotherapeutic intervention for managing opioid use disorder.
DESIGN: A 2 × 2 factorial, repeated-measures, open-label, randomized clinical trial.
SETTINGS: General medical practice offices in Muar, Malaysia.
PARTICIPANTS: Opioid-dependent individuals (n = 234).
INTERVENTIONS: Participants were randomly assigned to one of four treatment conditions and received study interventions for 24 weeks: (1) physician management with or without behavioral counseling and (2) physician management with or without abstinence-contingent buprenorphine-naloxone (ACB) take-home doses.
MEASUREMENTS: The primary outcomes were proportions of opioid-negative urine tests and HIV risk behaviors [assessed by audio computer-assisted AIDS risk inventory (ACASI-ARI)].
FINDINGS: The rates of opioid-negative urine tests over 24 weeks of treatment were significantly higher with [68.2%, 95% confidence interval (CI) = 65-71] than without behavioral counseling (59.2%, 95% CI = 56-62, P
Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.
Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.
Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.
Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.