Adenosine A(1) receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release.

BACKGROUND: Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. METHODS: Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8-cyclopentylxanthine. RESULTS: First, SPA significantly decreased respiratory rate (-18%), tidal volume (-12%), and minute ventilation (-16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. CONCLUSIONS: Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

Electroconvulsive Therapy for the Treatment of Severe Mood Disorders During Adolescence: A Retrospective Chart Review.

Objective: Electroconvulsive therapy (ECT) is a well-recognized treatment of refractory mood disorders in adults. However, relatively little is known about its use for similar conditions in adolescents. Based on a chart review, we describe its use and outcome in a sample of adolescents with severe, refractory mood disorders (unipolar or bipolar disorder) hospitalized in an academic medical center. Methods: The sample was drawn from referrals to an adolescent psychiatry service. After obtaining approval from the ethics board, medical records of 54 adolescents with refractory mood disorder were examined. Participants (males 24, females 30; mean age 15.8 ± 1.5 years) had received their first course of ECT before the age of 18 years during the period 1996-2010. Response to treatment was examined after the initial treatment and during a 1-year follow-up. Results: Following the index course of ECT (mean number of treatments = 13.7 ± 6.3), a 52.8% response rate (defined as a Clinical Global Impressions [CGI] score ≤2) was noted, while 15.1% achieved remission (CGI = 1). The response rate was 82.4% after a 1-year follow-up with a remission rate of 23.5%. The Children's Depression Rating scores declined significantly from pre-ECT to the end of the index course (70.7 ± 16.4 to 52.5 ± 18; p ≤ 0.00). A reduction in suicidal ideation and self-injurious behaviors along with increased school attendance was noted. Cognition, monitored by the Mini-Mental State Examination, did not decline significantly. Minor side effects were limited to the day of the treatment. Prolonged seizures (>2 minutes) were common during ECT (74% of subjects experienced one or more). The only side effect noted at the 1-year follow-up was self-reported memory loss involving events during and around the index treatment course. Conclusions: In this severely impaired sample of adolescents, ECT was found to decrease suicidal behavior, reduce depressive symptoms, and improve overall functioning, as indexed by school attendance at follow-up after 1 year. Prospective studies using large samples are needed to determine its effectiveness and safety in refractory mood disorders in adolescents.