Conditioned place preference for social interaction in rats: contribution of sensory components

A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus “social interaction” contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm2 prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus “social interaction” is touch (taction)

Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction

Antidepressant efficacy is correlated with plasma levels: mega-analysis and further evidence

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Le dosage plasmatique des médicaments psychotropes à des fins thérapeutiques: recommandations du groupe d'experts AGNP-TDM

In psychiatry, therapeutic drug monitoring (TDM) is an established procedure for most psychotropic drugs. However, as its use in everyday clinical practice is far from optimal, the AGNP-TDM group has worked out consensus guidelines to assist psychiatrists and laboratories involved in drug analysis. Based on a thorough analysis of available literature, 5 levels of recommendation were defined with regard to TDM of psychoactive drugs, from 1) (strongly recommended) to 5) (not recommended). A list of indications for TDM, alone or in combination with pharmacogenetic tests is presented. Instructions are given with regard to preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM. [References: 75]]]> fre oai:serval.unil.ch:BIB_2D18D21C9C20 2022-05-07T01:13:59Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_2D18D21C9C20 Effect of nutritive and non-nutritive sweeteners on hemodynamic responses to acute stress: a randomized crossover trial in healthy women. info:doi:10.1038/s41387-019-0104-y info:eu-repo/semantics/altIdentifier/doi/10.1038/s41387-019-0104-y info:eu-repo/semantics/altIdentifier/pmid/32066654 Cros, J. Bidlingmeyer, L. Rosset, R. Seyssel, K. Crézé, C. Stefanoni, N. Schneiter, P. Tappy, L. info:eu-repo/semantics/article article 2020-01-02 Nutrition &amp; diabetes, vol. 10, no. 1, pp. 1 info:eu-repo/semantics/altIdentifier/eissn/2044-4052 urn:issn:2044-4052 <![CDATA[The mechanisms by which chronic stress increases the risk of non-communicable diseases remain poorly understood. On one hand, chronic stress may increase systemic vascular resistance (SVR) and blood pressure, which may lead to blood vessels injury and altered myocardial perfusion. On the other hand, chronic stress may promote the overconsumption of sugar-containing foods and favor obesity. There is indeed evidence that sweet foods are preferentially consumed to alleviate stress responses. The effects of nutritive and non-nutritive sweeteners (NNS) on hemodynamic stress responses remain however largely unknown. This study aimed at comparing the effects of sucrose-containing and NNS-containing drinks, as compared to unsweetened water, on hemodynamic responses to acute stress in twelve healthy female subjects. Acute stress responses were elicited by a 30-min mental stress (5-min Stroop's test alternated with 5-min mental arithmetic) and a 3-min cold pressure test (CPT), each preceded by a resting baseline period. Hemodynamic stress responses were investigated by the repeated measurement of mean arterial pressure and the continuous monitoring of cardiac output by thoracic electrical bioimpedance measurement. SVR was selected as a primary outcome because it is a sensitive measure of hemodynamic responses to acute stress procedures. With all three drinks, SVR were not changed with mental stress (P = 0.437), but were increased with CPT (P = 0.045). Both mental stress and CPT increased mean arterial pressure and heart rate (all P &lt; 0.001). Cardiac output increased with mental stress (P &lt; 0.001) and remained unchanged with CPT (P = 0.252). No significant differences in hemodynamic responses were observed between water, sucrose and NNS (stress × condition, all P &gt; 0.05). These results demonstrate that sucrose and NNS do not alter hemodynamic responses to two different standardized acute stress protocols

The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants

Therapeutic drug monitoring (TDM) of psychotropic drugs such as antidepressants has been widely introduced for optimization of pharmacotherapy in psychiatric patients. The interdisciplinary TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has worked out consensus guidelines with the aim of providing psychiatrists and TDM laboratories with a tool to optimize the use of TDM. Five research-based levels of recommendation were defined with regard to routine monitoring of drug plasma concentrations: (i) strongly recommended; (ii) recommended; (iii) useful; (iv) probably useful; and (v) not recommended. In addition, a list of indications that justify the use of TDM is presented, eg, control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning drug metabolism, and children, adolescents, and elderly patients. For some drugs, studies on therapeutic ranges are lacking, but target ranges for clinically relevant plasma concentrations are presented for most drugs, based on pharmacokinetic studies reported in the literature. For many antidepressants, a thorough analysis of the literature on studies dealing with the plasma concentration–clinical effectiveness relationship allowed inclusion of therapeutic ranges of plasma concentrations. In addition, recommendations are made with regard to the combination of pharmacogenetic (phenotyping or genotyping) tests with TDM, Finally, practical instructions are given for the laboratory practitioners and the treating physicians how to use TDM: preparation of TDM, drug analysis, reporting and interpretation of results, and adequate use of information for patient treatment. TDM is a complex process that needs optimal interdisciplinary coordination of a procedure implicating patients, treating physicians, clinical pharmacologists, and clinical laboratory specialists. These consensus guidelines should be helpful for optimizing TDM of antidepressants

Differential Effects of Accumbens Core vs. Shell Lesions in a Rat Concurrent Conditioned Place Preference Paradigm for Cocaine vs. Social Interaction

A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. Among these activities, social interaction is doubly important because treatment adherence itself depends on it. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male conspecific (i) reversed CPP from cocaine to social interaction despite continuing cocaine training and (ii) prevented the reinstatement of cocaine CPP. In the present study, we investigated if the two subregions of the nucleus accumbens (Acb), i.e., the core (AcbC) and the shell (AcbSh), would differentially affect CPP for cocaine vs social interaction.Animals were concurrently trained for CPP pairing cocaine with one compartment and social interaction with the other (i.e., mutually exclusive stimulus presentation during training). Excitotoxic lesioning of the AcbC or the BLA shifted CPP toward social interaction, whereas AcbSh inactivation shifted CPP toward cocaine.Overall, our findings suggest that inactivation of the AcbC or the BLA is sufficient to shift CPP away from a drug of abuse toward social interaction. Lesioning the AcbSh produced the opposite effect

Systematic review and meta-analysis on the therapeutic reference range for escitalopram: Blood concentrations, clinical effects and serotonin transporter occupancy

IntroductionA titration within a certain therapeutic reference range presupposes a relationship between the blood concentration and the therapeutic effect of a drug. However, this has not been systematically investigated for escitalopram. Furthermore, the recommended reference range disagrees with mean steady state concentrations (11–21 ng/ml) that are expected under the approved dose range (10–20 mg/day). This work systematically investigated the relationships between escitalopram dose, blood levels, clinical effects, and serotonin transporter occupancy.MethodsFollowing our previously published methodology, relevant articles were systematically searched and reviewed for escitalopram.ResultsOf 1,032 articles screened, a total of 30 studies met the eligibility criteria. The included studies investigated escitalopram blood levels in relationship to clinical effects (9 studies) or moderating factors on escitalopram metabolism (12 studies) or serotonin transporter occupancy (9 studies). Overall, the evidence for an escitalopram concentration/effect relationship is low (level C).ConclusionBased on our findings, we propose a target range of 20–40 ng/ml for antidepressant efficacy of escitalopram. In maintenance treatment, therapeutic response is expected, when titrating patients above the lower limit. The lower concentration threshold is strongly supported by findings from neuroimaging studies. The upper limit for escitalopram’s reference range rather reflects a therapeutic maximum than a tolerability threshold, since the incidence of side effects in general is low. Concentrations above 40 ng/ml should not necessarily result in dose reductions in case of good clinical efficacy and tolerability. Dose-related escitalopram concentrations in different trials were more than twice the expected concentrations from guideline reports.Systematic review registration[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=215873], identifier [CRD42020215873]

Handbooks of pharmacology and toxicology

The overwhelming majority of problem drinkers (i.e., alcohol-abusing patients) and alcohol-dependent patients are first seen by physicians in general practice, in a primary care setting, or at nonpsychiatric inpatient facilities, such as departments of internal medicine or surgery. If you work in such a setting, this book is for you. It is my firm belief that comprehensive treatment of your alcohol-abusing or alcohol-dependent patient lies within your grasp and should, for that matter, ultimately lie in the hands of one therapist; this book will help you to acquire the necessary expertise to achieve this. You will, in all likelihood, find that you want to delegate some aspects of the medical care of your alcoholic patient to more specialized partners who might have more resources than you with respect to time, logistics, and specialized training. Still, it is you who can give crucial help to your patient who is experiencing alcohol-related problems, right from the first contact and interview. And, let’s face it, you have to do it — you are the one your patient usually first contacts and not necessarily because he or she is aware of her/his alcohol problem. Not yet. With the help of this handbook, you will acquire the necessary skills to help him/her recognize the underlying alcohol problem. Two chapters (Chapter 1, First Contact and Early Intervention; Chapter 9, Psychotherapy) are dedicated to explaining which psychological problems you are most likely to encounter at every stage of the disease and how to best cope with the negative emotions that the alcohol-dependent patient — so severely affected by the disease — will most likely induce in you, his physician