Withdrawal effect of chronic amphetamine exposure during adolescence on complex maze performance.

National survey data suggest a steady increase in the diagnosis and treatment of mental disorders in children, particularly Attention Deficit/Hyperactivity Disorder (ADHD). As nearly all children diagnosed with ADHD are prescribed stimulant drugs, rationale exists to quantitatively characterize behavioral responses following withdrawal from chronic stimulant dosing. These rodent experiments involved chronic administration of 7.5 mg/kg, s.c. amphetamine to subjects throughout adolescence followed by cognitive tests to gauge learning and performance during the withdrawal stage 7 to 14 days past withdrawal. Tests used a complex Stone 14-unit multiple T-maze, which is a robust paradigm for demonstrating age-related differences in rodent models when behavioral cognitive endpoints are used. Results reveal that amphetamine-treated subjects committed fewer major and retracing errors with increased minor errors and a significantly lower mean completion time. These findings suggest that pharmacotherapy aimed at adolescent-phase treatment of ADHD does not provoke spatial memory deficits at times proximal to drug withdrawal and lends support to amphetamine use in the treatment of ADHD children.

A preliminary study of silicone hydrogel lens material and care solution bioincompatibilities.

PURPOSE: The study purpose was to evaluate corneal barrier function and staining relative to potential bioincompatibilities. METHODS: This was a randomized double-masked study (n = 25 subjects). Three lens material-care solution combinations were tested: (1) lotrafilcon B/polyhexamethylene biguanide (PHMB)-based multipurpose (MPS) solution (MPS-1); (2) lotrafilcon B/polyquaternium-1 and myristamidopropyl dimethylamine-based solution (MPS-2); and (3) lotrafilcon B and another PHMB-based solution (MPS-3). Saline served as the control. New lenses were soaked in the preserved solutions or saline and then worn for 2 hours before corneal measurements. Barrier function was characterized by the fluorescein penetration rate, corneal amount, both measured with an objective scanning fluorometer. The dye penetration rate ratio, test to control; amount ratio, test to control, and corneal staining were evaluated. RESULTS: The mean rate ratios (± SD) for the combinations were 2.98 (± 3.04), 1.23 (± 1.01), and 1.83 (± 1.77) for MPS-1, MPS-2, and MPS-3 solutions, respectively. Significant ratio differences were found across regimens (P = 0.007); for MPS-1 compared with baseline (P = 0.031) and for MPS-1 compared with MPS-2 (P = 0.007). The statistical results for staining were similar. CONCLUSIONS: Use of an objective quantitative physiological method suggests that significant differences in lens solution bioincompatibilities occur that mirror corneal staining data relative to corneal compromise.

The hallucinogen derived from Salvia divinorum, salvinorin A, has kappa-opioid agonist discriminative stimulus effects in rats.

Data from clinical and preclinical studies converge implicating the plant-derived hallucinogen salvinorin A as an important pharmacologic tool; this psychoactive compound may expand scientific understandings on mammalian kappa-opioid receptor systems. Human salvinorin A effects, consistent with kappa-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted perceptions. The experiments reported here measured salvinorin A (1-3mg/kg, i.p.) discriminative stimulus properties in male Sprague-Dawley rats conditioned to recognize the discriminative stimulus cue generated by the well characterized kappa-opioid agonist U-69593 (0.56 mg/kg, i.p.). At three distinct active doses, salvinorin A fully substituted for U-69593 without altering response rates. The lever choice pattern in U-69593 trained animals reverted to vehicle lever responding when a kappa selective antagonist compound, nor-BNI (4.5 nM, i.c.v.) was administered 1h prior to salvinorin A, yet nor-BNI alone failed to impact the rate or pattern of subject responses. These findings confirm and extend results published after similar drug discrimination tests were performed in rhesus monkeys. The discussion section of this article highlights public concern over salvinorin A misuse and emphasizes several potential pharmacotherapeutic applications for salvinorin A or analogue compounds.