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Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces quick and effective antidepressant results in depressed juvenile and adult individuals. The long-term consequences of using ketamine in juvenile populations are not well known, particularly as it affects vulnerability to drugs of abuse later in life, given that ketamine is also a drug of abuse. Thus, the current study examined whether early-life ketamine administration produces long-term changes in the sensitivity to the rewarding effects of ethanol, as measured using the conditioned place preference (CPP) paradigm. On postnatal day (PD) 21, juvenile male and female rats were pretreated with ketamine (0.0 or 20 mg/kg) for 10 consecutive days (i.e., PD 21-30) and then evaluated for ethanol-induced CPP (0.0, 0.125, 0.5, or 2.0 g/kg) from PD 32-39. Results revealed that early-life ketamine administration attenuated the rewarding properties of ethanol in male rats, as ketamine pretreated rats failed to exhibit ethanol-induced CPP at any dose compared to saline pretreated rats, which showed an increased preference towards the ethanol-paired compartment in a dose-dependent manner. In females, ethanol-induced CPP was generally less robust compared to males, but ketamine pretreatment resulted in a rightward shift in the dose-response curve, given that ketamine pretreated rats needed a higher dose of ethanol compared to saline pretreated rats to exhibit ethanol-induced CPP. When considered together, the findings suggest that early use of ketamine does not appear to enhance the vulnerability to ethanol later in life, but in contrast, it may attenuate the rewarding effects of ethanol.

In this computational study we analyze segregated population of ions in biological tissues and how electric or magnetic fields can relocate them. The appropriate definition of a segregated population of ions is justified for its physiological relevance, algorithmic simplicity and biophysical realism. Although this study can be valid for several ions and cell compartments, we focus on calcium ions in parallel dendrites of neurons. Computer simulations are presented as calcium flux visualizations showing the final position of each ion in different conditions in neurons: in the absence of an electric field and in the presence of it at different timings in relation to the initial release event of calcium into the dendrites. The simulation suggests that it is possible to relocate (probabilistically) aggregations of calcium ions in the spaces of the dendrites, allowing neuromodulation of synaptic connections. In conclusion, the maximal response to endogenous electric fields and the efficient way to design “friendly” devices for electrical field stimulation of neurons for relocating calcium ions close to their targets (e.g. vesicle sensors, proteins in membranes, or cytosol) depends on the geometry of dendrites, the duration and timing of the field (respect to ongoing activity), and the selection of the appropriate subpopulation we want to relocate.

Long fibers assembled from peptide amphiphiles capable of binding the metalloporphyrin zinc protoporphyrin IX ((PPIX)Zn) have been synthesized. Rational peptide design was employed to generate a peptide, c16-AHL(3)K(3)-CO(2)H, capable of forming a β-sheet structure that propagates into larger fibrous structures. A porphyrin-binding site, a single histidine, was engineered into the peptide sequence in order to bind (PPIX)Zn to provide photophysical functionality. The resulting system indicates control from the molecular level to the macromolecular level with a high order of porphyrin organization. UV/visible and circular dichroism spectroscopies were employed to detail molecular organization, whereas electron microscopy and atomic force microscopy aided in macromolecular characterization. Preliminary picosecond transient absorption data are also reported. Reduced hemin, (PPIX)Fe(II), was also employed to highlight the material's versatility and tunability.

Synaptic transmission throughout most of the CNS is steeply dependent on presynaptic calcium influx through the voltage-gated calcium channels Cav2.1–Cav2.3. In addition to triggering exocytosis, this calcium influx also recruits short-term synaptic plasticity. During the complex patterns of presynaptic activity that occur in vivo, several forms of plasticity combine to generate a synaptic output that is dynamic, in which the size of a given excitatory postsynaptic potential (EPSP) in response to a given spike depends on the short-term history of presynaptic activity. It remains unclear whether the different Cav2 channels play distinct roles in defining these synaptic dynamics and, if so, under what conditions different Cav2 family members most effectively determine synaptic output. We examined these questions by measuring the effects of calcium channel-selective toxins on synaptic transmission at the Schaffer collateral synapse in hippocampal slices from adult mice in response to both low-frequency stimulation and complex stimulus trains derived from in vivo recordings. Blockade of Cav2.1 had a greater inhibitory effect on synaptic transmission during low-frequency components of the stimulus train than on synaptic transmission during high-frequency components of the train, indicating that Cav2.1 had a greater fractional contribution to synaptic transmission at low frequencies than at high frequencies. Relative to Cav2.1, Cav2.2 had a disproportionately reduced contribution to synaptic transmission at frequencies >20 Hz, while Cav2.3 had a disproportionately increased contribution to synaptic transmission at frequencies >1 Hz. These activity-dependent effects of different Cav2 family members shape the filtering characteristics of GABAB receptor-mediated presynaptic inhibition. Thus different Cav2 channels vary in their coupling to synaptic transmission over different frequency ranges, with consequences for the frequency tuning of both synaptic dynamics and presynaptic neuromodulation.

Drug abuse and addiction are major problems in the United States. In particular methamphetamine (METH) use has increased dramatically. A greater understanding of how METH acts on the brain to induce addiction may lead to better therapeutic targets for this problem. The hippocampus is recognized as an important structure in learning and memory, but is not typically associated with drug reinforcement or reward processes. Here, the focus is on the hippocampus which has been largely ignored in the addiction literature as compared to the nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC). The results show that METH administered unilaterally via a microdialysis probe to rats’ right dorsal hippocampus will induce drug-seeking (place preference) and drug-taking (lever-pressing) behavior. Furthermore, both of these responses are dependent on local dopamine (DA) receptor activation, as they are impaired by a selective D1/D5 receptor antagonist. The results suggest that the hippocampus is part of the brain’s reward circuitry that underlies addiction.