Acute Ketamine Facilitates Fear Memory Extinction in a Rat Model of PTSD Along With Restoring Glutamatergic Alterations and Dendritic Atrophy in the Prefrontal Cortex

Stress represents a major risk factor for psychiatric disorders, including post-traumatic stress disorder (PTSD). Recently, we dissected the destabilizing effects of acute stress on the excitatory glutamate system in the prefrontal cortex (PFC). Here, we assessed the effects of single subanesthetic administration of ketamine (10 mg/kg) on glutamate transmission and dendritic arborization in the PFC of footshock (FS)-stressed rats, along with changes in depressive, anxious, and fear extinction behaviors. We found that ketamine, while inducing a mild increase of glutamate release in the PFC of na\uefve rats, blocked the acute stress-induced enhancement of glutamate release when administered 24 or 72 h before or 6 h after FS. Accordingly, the treatment with ketamine 6 h after FS also reduced the stress-dependent increase of spontaneous excitatory postsynaptic current (sEPSC) amplitude in prelimbic (PL)-PFC. At the same time, ketamine injection 6 h after FS was found to rescue apical dendritic retraction of pyramidal neurons induced by acute stress in PL-PFC and facilitated contextual fear extinction. These results show rapid effects of ketamine in animals subjected to acute FS, in line with previous studies suggesting a therapeutic action of the drug in PTSD models. Our data are consistent with a mechanism of ketamine involving re-establishment of synaptic homeostasis, through restoration of glutamate release, and structural remodeling of dendrites

Combining Logics to Transform Organizational Agency: Blending Industry and Art at Alessi

To understand how organizations combine conflicting institutional logics strategically to create and pursue new market opportunities, we conducted an in-depth longitudinal study of the multiple efforts of the Italian manufacturer of household goods Alessi to combine the logics of industrial manufacturing and cultural production. Over three decades, Alessi developed three different strategies to combine normative elements of the two logics, using each strategy to envision and pursue different market opportunities. By combining the logics of industrial manufacturing and cultural production, Alessi was able to envision new possibilities for value creation and to enact them through innovation in product design. The three strategies triggered a common set of mechanisms through which the purposeful combining of logics enabled the pursuit of opportunity, while each strategy structured the process differently. We develop a theoretical model linking the development of recombinant strategies to the dynamic restructuring of organizational agency and the related capacity to create and pursue new market opportunities. Our findings and theoretical insights advance understanding of the processes through which organizations challenge taken-for-granted beliefs and practices to create new market opportunities, use logics as resources to enable embedded agency, and design hybrid organizational arrangements

Black earths from Veneto and Piedmont (Northern Italy): origin, composition and potential use in different painting techniques

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Sexual Functioning and Opioid Maintenance Treatment in Women. Results From a Large Multicentre Study

Opioid maintenance treatment (OMT) is the most widespread therapy for both females and males opioid addicts. While many studies have evaluated the OMT impact on men’s sexuality, the data collected about the change in women’s sexual functioning is still limited despite the fact that it is now well-known that opioids - both endogenous and exogenous - affect the endocrine system and play an important role in sexual functioning. The present study aims to determine how OMT with buprenorphine (BUP) or methadone (MTD) affects sexual health in women; examining also any possible emerging correlation between sexual dysfunction (SD), type of opioid and patients’ mental health. This multi-center study case recruited 258 female volunteers attending Italian public Addiction Outpatients Centers that were stabilized with OMT for at least 3 months. SD was assessed with the Arizona Sexual Experience Scale. The twelve-item General Health Questionnaire was used to assess participants’ mental health conditions. The results show that 56.6% of women receiving OMT for at least 3 months presented SD without significant differences between MTD e BUP groups. The majority of the subjects with SD have a poorer quality of intimate relationships and worse mental health than the average. To the best of our knowledge, the present study is the largest report on the presence of SDs in women as a side effects of MTD and BUP used in OMT. Since SDs cause difficulties in intimate relationships, lower patients’ quality of life and interfere with OMT beneficial outcomes, we recommend that women undertaking an opioid therapy have routine screening for SD and we highlight the importance to better examine opioid-endocrine interactions in future studies in order to provide alternative potential treatments such as the choice of opioid, opioid dose reduction and hormone supplementation

Ketamine alters excitatory synaptic currents in the medial prefrontal cortex of acutely stressed rats

Ketamine alters excitatory synaptic currents in the medial prefrontal cortex of acutely stressed rats E. SCHIAVON1, F. SALERNO SCARZELLA1, L. MUSAZZI2, M. POPOLI2, L. FORTI1. 1Dept. of Biotech. and Life Sci., Univ. of Insubria, Busto Arsizio, Italy; 2Dept. Pharmacol. and Biomolecular Sci., Univ. degli Studi di Milano, Milano, Italy Abstract: The cellular and functional changes underlying the adaptive or maladaptive behavioral effects of an acute stressor are not well understood. In the medial prefrontal cortex (mPFC) of male rats, 40 min foot-shock protocol (FS), rapidly (~1 hr) increases the number of excitatory synapses, the readily releasable Glu vesicle pool in synaptosomes, and the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) recorded in L2/3 pyramidal neurons (Pyr). Within 24 hrs, FS induces shrinkage of apical dendrites, while no information exists for sEPSCs. Miniature excitatory synaptic currents (mEPSCs) have been suggested to have a neurotrophic and homeostatic role, but the effects of FS on mEPSCs are unknown. To understand the sustained effects of FS on Glu transmission in the mPFC and its regulation by ketamine at antidepressant dosage, synaptic currents were recorded 24 hrs after FS in visually identified layer 2/3 Pyr of prelimbic mPFC in slices from adult male rats. Animals subjected to a 40-min session of inescapable FS (FS group), animals injected with ketamine (10mg/kg) 6 hrs after FS, and controls (CTR) were compared. The amplitude, area, rise, decay, and inter-event intervals of mEPSCs and sEPSCs were analyzed. mEPSCs in the FS group showed a tendency to minor changes in frequency (small increase) and ampitude (small decrease) vs CTR. Ketamine after FS increased mEPSC frequency and peak amplitude and accelerated rise and decay with no change in area, as compared to CTR. sEPSCs frequency in the FS group had a tendency to a small decrease, with no change in waveform vs CTR. Ketamine after FS produced similar effects on sESPCs as for mEPSCs. Overall, this work indicates that, 24 hrs after FS, no or minor changes occur in miniature and spontaneous synaptic currents at layer 2/3 excitatory synapses of the mPFC. Ketamine modulation of the Glu synaptic currents of stressed animals suggests changes in synapse morphology and/or dendritic localization