UDS on the 82 oncology patients at high risk for substance misuse were frequently positive (46%) for non-prescribed opioids, benzodiazepines or potent illicit drugs such as heroin or cocaine, and 39% had inappropriately negative UDS, raising concerns for diversion.

Dopamine acts through dopamine type 1 receptors (comprised of D1 and D5 subtypes) and dopamine type 2 receptors (comprised of D2, D3 and D4 subtypes). Intracranial self-stimulation (ICSS) is one experimental procedure that can be used to evaluate abuse-related effects of drugs targeting dopamine receptors. This study evaluated effects of dopamine receptor ligands on ICSS in rats using experimental procedures that have been used previously to examine abused indirect dopamine agonists such as cocaine and amphetamine. Male Sprague-Dawley rats responded under a fixed-ratio 1 schedule for electrical stimulation of the medial forebrain bundle, and frequency of stimulation varied from 56–158 Hz in 0.05 log increments during each experimental session. Drug potency and time course were determined for the D1 ligands A77636, SKF82958, SKF38393, fenoldopam and SCH39166 and the D2/3 ligands sumanirole, apomorphine, quinpirole, PD128907, pramipexole, aripiprazole, eticolopride and PG01037. The high-efficacy D1 agonists A77636 and SKF82958 produced dose-dependent, time-dependent, and abuse-related facilitation of ICSS. Lower efficacy D1 ligands and all D2/3 ligands failed to facilitate ICSS at any dose or pretreatment time. A mixture of SKF82958 and quinpirole produced a mixture of effects produced by each drug alone. Quinpirole also failed to facilitate ICSS after regimens of repeated treatment with either quinpirole or cocaine. These studies provide more evidence for divergent effects of dopamine D1- and D2-family agonists on ICSS procedure in rats and suggest that ICSS may be a useful complement to other approaches for preclinical abuse potential assessment, in part because of the reproducibility of results.

No abstract

Paclitaxel is a cancer chemotherapy with adverse effects that include peripheral neuropathy, neuropathic pain, and depression of behavior and mood. In rodents, hypersensitive paw-withdrawal reflexes from mechanical stimuli serve as one common measure of paclitaxel-induced pain-related behavior. This study tested the hypothesis that paclitaxel would also depress rates of positively reinforced operant responding as a measure of pain-related behavioral depression. Male and female Sprague-Dawley rats were equipped with electrodes targeting the medial forebrain bundle, trained to lever press for electrical brain stimulation in an assay of intracranial self-stimulation (ICSS), and treated with four injections of varying paclitaxel doses (0.67, 2.0, or 6.0 mg/kg/injection×4 injections on alternate days). Mechanical sensitivity, body weight, and ICSS were evaluated before, during, and for 3 weeks after paclitaxel treatment. Paclitaxel doses sufficient to produce mechanical hypersensitivity did not reliably depress ICSS in male or female rats. Moreover, the degree of behavioral suppression in individual rats did not correlate with mechanical sensitivity. Paclitaxel treatment regimens commonly used to model chemotherapy-induced neuropathic pain in rats are not sufficient to depress ICSS.