Detection of Single Ion Spectra by Coulomb Crystal Heating

The coupled motion of ions in a radiofrequency trap has been used to connect the frequency- dependent laser-induced heating of a sympathetically cooled spectroscopy ion with changes in the fluorescence of a laser-cooled control ion. This technique, sympathetic heating spectroscopy, is demonstrated using two isotopes of calcium. In the experiment, a few scattered photons from the spectroscopy ion are transformed into a large deviation from the steady-state fluorescence of the control ion. This allows us to detect an optical transition where the number of scattered photons is below our fluorescence detection limit. Possible applications of the technique to molecular ion spectroscopy are briefly discussed.Comment: 7 Pages,10 Figure

Stressor- and Corticotropin releasing Factor-induced Reinstatement and Active Stress-related Behavioral Responses are Augmented Following Long-access Cocaine Self-administration by Rats

Rationale Stressful events during periods of drug abstinence likely contribute to relapse in cocaine-dependent individuals. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) responsiveness. Objectives This study examined stressor- and CRF-induced cocaine seeking and other stress-related behaviors in rats with different histories of cocaine self-administration (SA). Materials and methods Rats self-administered cocaine under short-access (ShA; 2 h daily) or long-access (LgA; 6 h daily) conditions for 14 days or were provided access to saline and were tested for reinstatement by a stressor (electric footshock), cocaine or an icv injection of CRF and for behavioral responsiveness on the elevated plus maze, in a novel environment and in the light–dark box after a 14- to 17-day extinction/withdrawal period. Results LgA rats showed escalating patterns of cocaine SA and were more susceptible to reinstatement by cocaine, EFS, or icv CRF than ShA rats. Overall, cocaine SA increased activity in the center field of a novel environment, on the open arms of the elevated plus maze, and in the light compartment of a light–dark box. In most cases, the effects of cocaine SA were dependent on the pattern/amount of cocaine intake with statistically significant differences from saline self-administering controls only observed in LgA rats. Conclusions When examined after several weeks of extinction/ withdrawal, cocaine SA promotes a more active pattern of behavior during times of stress that is associated with a heightened susceptibility to stressor-induced cocaine-seeking behavior and may be the consequence of augmented CRF regulation of addiction-related neurocircuitry

Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

International audienceBACKGROUND:There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.METHODOLOGY/PRINCIPAL FINDINGS:Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.CONCLUSIONS/SIGNIFICANCE:Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders

Corticotropin Releasing Factor-Induced CREB Activation in Striatal Neurons Occurs via a Novel Gβγ Signaling Pathway

The peptide corticotropin-releasing factor (CRF) was initially identified as a critical component of the stress response. CRF exerts its cellular effects by binding to one of two cognate G-protein coupled receptors (GPCRs), CRF receptor 1 (CRFR1) or 2 (CRFR2). While these GPCRs were originally characterized as being coupled to Gαs, leading to downstream activation of adenylyl cyclase (AC) and subsequent increases in cAMP, it has since become clear that CRFRs couple to and activate numerous other downstream signaling cascades. In addition, CRF signaling influences the activity of many diverse brain regions, affecting a variety of behaviors. One of these regions is the striatum, including the nucleus accumbens (NAc). CRF exerts profound effects on striatal-dependent behaviors such as drug addiction, pair-bonding, and natural reward. Recent data indicate that at least some of these behaviors regulated by CRF are mediated through CRF activation of the transcription factor CREB. Thus, we aimed to elucidate the signaling pathway by which CRF activates CREB in striatal neurons. Here we describe a novel neuronal signaling pathway whereby CRF leads to a rapid Gβγ- and MEK-dependent increase in CREB phosphorylation. These data are the first descriptions of CRF leading to activation of a Gβγ-dependent signaling pathway in neurons, as well as the first description of Gβγ activation leading to downstream CREB phosphorylation in any cellular system. Additionally, these data provide additional insight into the mechanisms by which CRF can regulate neuronal function

EEG Biofeedback as a Treatment for Substance Use Disorders: Review, Rating of Efficacy, and Recommendations for Further Research

Electroencephalographic (EEG) biofeedback has been employed in substance use disorder (SUD) over the last three decades. The SUD is a complex series of disorders with frequent comorbidities and EEG abnormalities of several types. EEG biofeedback has been employed in conjunction with other therapies and may be useful in enhancing certain outcomes of therapy. Based on published clinical studies and employing efficacy criteria adapted by the Association for Applied Psychophysiology and Biofeedback and the International Society for Neurofeedback and Research, alpha theta training—either alone for alcoholism or in combination with beta training for stimulant and mixed substance abuse and combined with residential treatment programs, is probably efficacious. Considerations of further research design taking these factors into account are discussed and descriptions of contemporary research are given

55 Methamphetamine-Induced Vaginal Lubrication & Associated Hormonal Changes

ABSTRACT Introduction Vaginal dryness is an issue that affects millions of women, creating a situation that often leads to painful sexual experiences and diminished pleasure and self-esteem. Though the physiology of vaginal lubrication in response to sexually arousing stimuli is established, no treatment, other than topical lubricants, is available for women suffering from vaginal dryness. Previous research from our lab reported that female methamphetamine (meth) users experience immediate and noticeable vaginal lubrication when they inject the drug intravenously (IV). A warming or flushing sensation spreading from the chest area down into the pelvic region accompanied this lubrication. Understanding the mechanisms mediating this previously undescribed phenomenon may reveal a potential target for future pharmaceutical development to enhance a woman's natural levels of vaginal lubrication. We have reported that injections of meth also increase vaginal lubrication in rats in a dose-dependent manner. Plasma levels of several signaling molecules known to influence vaginal lubrication, including the steroid hormones estradiol, progesterone, and testosterone, as well as the gaseous vasodilator nitric oxide, increase at specific time points following IV meth in female rats. Accordingly, we were able to decrease the amount of vaginal fluid produced by pre-treating the animals with the nitric oxide synthase inhibitor, L-NAME, prior to meth. Objective The present work expands the aforementioned findings by measuring plasma levels of vasoactive intestinal polypeptide (VIP), an established mediator of female sexual arousal, and corticosterone, a steroid hormone implicated in drug addiction, after IV injections of meth. We also determined the involvement of estradiol in meth-induced vaginal lubrication using an estrogen receptor antagonist. Methods We implanted adult female Wistar rats with chronic indwelling jugular catheters and allowed them at least one week to recover from surgery. We pre-treated the rats with fulvestrant, an estrogen receptor antagonist, and then anesthetized them with isoflurane gas before injecting them intravenously with meth via the implanted catheter. A pre-weighed cotton-tipped swab, inserted into the vaginal canal, collected fluid secreted following the administration of meth. The change in the weight of the swab before and after meth indicated the amount of fluid produced. In a separate group of rats, we used the jugular catheter to remove blood at various time points (1-60 min) following the meth injections to measure plasma levels of VIP and corticosterone. Results Although we have not yet completed these experiments, we hypothesize that the inhibition of estrogen receptors will reduce meth-induced vaginal lubrication similar to the reduction produced by L-NAME. Further, we predict that both VIP and corticosterone levels will increase between 5 and 20 min after the injections of meth, similarly to the other signaling molecules we measured previously. Conclusions These findings have far-reaching and potentially life-changing implications, as the majority of women will experience vaginal dryness a least once in their lifetimes, if not chronically. The underlying mechanisms of meth-induced vaginal lubrication may provide the necessary pharmacological target to treat vaginal dryness. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Goeders is on the Scientific Advisory Boards for Embera NeuroTherapeutics and JanOne; however, the work of these companies is unrelated to the submitted abstract. </jats:sec