Garrett Sparks

Effects of m-CPP in Altering Neuronal Function: Blocking Depolarization in Invertebrate Motor and Sensory Neurons but Exciting Rat Dorsal Horn Neurons

The compound m-chlorophenylpiperazine (m-CPP) is used clinically to manipulate serotonergic function, though its precise mechanisms of actions are not well understood. m-CPP alters synaptic transmission and neuronal function in vertebrates by non-selective agonistic actions on 5-HT(1) and 5-HT(2) receptors. In this study, we demonstrated that m-CPP did not appear to act through a 5-HT receptor in depressing neuronal function in the invertebrates (crayfish and Drosophila). Instead, m-CPP likely decreased sodium influx through voltage-gated sodium channels present in motor and primary sensory neurons. Intracellular axonal recordings showed that m-CPP reduced the amplitude of the action potentials in crayfish motor neurons. Quantal analysis of excitatory postsynaptic currents, recorded at neuromuscular junctions (NMJ) of crayfish and Drosophila, indicated a reduction in the number of presynaptic vesicular events, which produced a decrease in mean quantal content. m-CPP also decreased activity in primary sensory neurons in the crayfish. In contrast, serotonin produces an increase in synaptic strength at the crayfish NMJ and an increase in activity of sensory neurons; it produces no effect at the Drosophila NMJ. In the rat spinal cord, m-CPP enhances the occurrence of spontaneous excitatory postsynaptic potentials with no alteration in evoked currents.

Prospective longitudinal course of aggression among adults with bipolar disorder

Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross‐sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with BP compared with non‐BP patients and healthy controls.

Sensitivity and specificity of a procedure for early human screening of novel smoking cessation medications

BACKGROUND AND AIM It is important to find economical methods in early Phase 2 studies to screen drugs potentially useful to aid smoking cessation. A method has been developed that detects efficacy of varenicline and nicotine patch. This study aimed to evaluate whether the method would detect the efficacy of bupropion and identify correctly the lack of efficacy of modafinil. DESIGN Using a within-subject double cross-over design, smokers attempted to quit during each treatment, with bupropion (150 mg b.i.d.), modafinil [100 mg twice daily (b.i.d.)] or placebo (double-blind, counterbalanced order). In each of three medication periods, all smoked with no drug on week 1 (baseline or washout), began dose run-up on week 2, and tried to quit every day during week 3. SETTING A university research center in the United States. PARTICIPANTS Forty-five adult smokers high in quit interest. MEASUREMENTS Abstinence was verified daily each quit week by self-report of no smoking over the prior 24 hours and carbon monoxide (CO) < 5 parts per million. FINDINGS Compared with placebo, bupropion did (F(1,44)  = 6.98, P = 0.01), but modafinil did not (F(1,44)  = 0.29, P = 0.60), increase the number of abstinent days. Also, bupropion (versus placebo) significantly increased the number of those able to maintain continuous abstinence on all 5 days throughout the quit week (11 versus four), Z = 2.11, P < 0.05, while modafinil did not (six). CONCLUSIONS Assessing days abstinent during 1 week of use of medication versus placebo in a cross-over design could be a useful early Phase 2 study design for discriminating between medications useful versus not useful in aiding smoking cessation.

Training physicians for the real world of medicine: administration-based learning.

Tired of outdated teaching formats like case‐based learning (CBL), problem‐based learning (PBL) and team‐based learning (TBL)? We wanted something fresh for our medical school, something that would prepare our graduates for the modern practice of medicine, something that would satisfy regulatory agencies and our deans. After doing an extensive needs assessment, which we ignored, we decided to replace basic science in our curriculum with something more practical: administration‐based learning (ABL). We taught students how to fix fax machines, how to deal with angry team members, and how to maximise revenue in private practice – lessons that were well received and were more consistent with what physicians really need to learn to be effective practitioners. Educational outcomes have been positive, and although more research is needed, we call on other schools to add ABL tracks to their own curricula.