Background
Alcohol dependence is a complex psychiatric disorder demanding development of novel pharmacotherapies. Since the cyclic AMP (cAMP) signaling cascade has been implicated in mediating behavioral responses to alcohol, key components in this cascade may serve as potential treatment targets. Phosphodiesterase 4 (PDE4), an enzyme that specifically catalyzes the hydrolysis of cAMP, represents as a key point in regulating intracellular cAMP levels. Thus, it was of interest to determine whether PDE4 was involved in the regulation of alcohol use and abuse.
Methods
Male Fawn-Hooded (FH/Wjd) rats were tested for 5% (v/v) ethanol and 10% (w/v) sucrose operant oral self-administration following treatment with the selective PDE4 inhibitor rolipram (0.0125, 0.025, or 0.05 mg/kg, s.c.); rolipram at higher doses (0.05, 0.1, and 0.2 mg/kg, s.c.) was tested to determine its impact on the intake of ethanol, sucrose, or water using the two-bottle choice drinking paradigm. Subsequent open-field testing was performed to evaluate the influence of higher doses of rolipram on locomotor activity.
Results
Acute administration of rolipram dose-dependently reduced operant self-administration of 5% ethanol, but had no effect on 10% sucrose responding. Time-course assessment revealed significant decreases in ethanol consumption after rolipram (0.1, 0.2 mg/kg) treatment in continuous- and intermittent-access to ethanol at 5% or 10%, respectively. Moreover, chronic rolipram treatment time-dependently decreased 5% ethanol consumption and preference during treatment days and after the termination of rolipram administration. Rolipram at the highest doses (0.1 and 0.2 mg/kg) did decrease locomotor activity, but the effect lasted only 10 and 20 min, respectively, which did not likely alter long-term ethanol drinking.
Conclusions
These results suggest that PDE4 plays a role in alcohol seeking and consumption behavior. Drugs interfering with PDE4 may be a potential pharmacotherapy for alcohol dependence.
Purpose: Intrathecal morphine infusion therapy via a percutaneous port (IMITPP) has been used widely for its relatively low initial cost. However, there is scarce knowledge about IMITPP. In this study, we sought to evaluate efficacy, complications, and the interval required to achieve the cost equivalence of IMITPP in patients with refractory cancer pain in China. Patients and Methods: A retrospective chart review was conducted on cancer patients who had received IMITPP at our hospital between April 2017 and April 2019. Data from the numeric pain rating scale and Karnofsky performance scores, and complications and costs related to IMITPP were collected from medical records. Daily analgesic costs before and after IMITPP were calculated based on the doses of opioids on admission and at discharge, respectively. The doses of systemic opioids before IMITPP were stratified into very high doses [VHD, oral morphine equivalent dose (OMED) >599 mg/day], high doses (HD, 300 mg/day ≤ OMED ≤ 599 mg/day), and regular doses (RD, OMED < 300 mg/day). Results: Intrathecal morphine infusion therapy via a percutaneous port provided significant pain relief, but impaired activities of daily living in patients with refractory cancer pain. The commonly reported complications included nausea/vomiting and urinary retention, most of which were managed with symptomatic therapies. The median interval required to achieve cost equivalence was 11.44 months. The median intervals of VHD group and HD group were significantly shorter than that of RD group. Conclusion: Intrathecal morphine infusion therapy via a percutaneous port provided effective cancer pain management without causing serious complications. Patients with higher doses of systemic opioids would economically benefit from IMITPP in a shorter time.
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