Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice

Rationale  

Heavy binge drinking is increasingly frequent among adolescents, while ethanol (EtOH) is often used in combination with 3,4-methylenedioxymethamphetamine (MDMA).     

7-Nitroindazole blocks conditioned place preference but not hyperactivity induced by morphine

The effects of 7-nitroindazole (7-NI), a neural nitric oxide synthase (nNOS) inhibitor, on spontaneous locomotor activity, morphine-induced hyperactivity, acquisition of place conditioning and morphine-induced conditioned place preference (CPP) were evaluated in male mice. In experiment 1, animals treated with 7-NI (25, 50 and 100 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus 7-NI (25, 50 or 100 mg/kg) were placed in an actimeter for 3 h. In experiment 2, animals treated with the same drugs and doses were conditioned following an unbiased procedure. 7-NI did not affect the spontaneous locomotor activity or hyperactivity induced by morphine. However, the moderate and high doses of 7-NI produced conditioned place aversion (CPA) and the lowest dose blocked morphine-induced CPP. Our results suggest that nitric oxide is involved in the rewarding properties of morphine but not in its motor effects.     

Subcutaneous sarcoidosis associated with vitiligo, pernicious anaemia and autoimmune thyroiditis

We report a patient with pernicious anaemia, primary autoimmune hypothyroidism and vitiligo, who presented with subcutaneous nodules. Histopathology of the nodules revealed noncaseating granulomas, consistent with a diagnosis of sarcoidosis. Mild pulmonary sarcoid was also detected. Although an association between sarcoidosis and other autoimmune diseases is well-recognized, the presence of the particular autoimmune diseases in our patient and the involvement of subcutaneous fat in the sarcoidal inflammation, appears to represent a most unusual clinicopathological combination.     

The dopamine D3 antagonist U-99194A maleate increases social behaviors of isolation-induced aggressive male mice

Rationale: Blockade of D₁/D₂ dopamine receptors produce an antiaggressive action commonly associated with an impairment of other motor behaviors. The D₃ receptor seems to present opposite actions to the D₁ and D₂, since the blockade of this receptor produces stimulation of motor activity which has been associated with an increase in dopamine neurotransmission. Objective: In this work, the action of the dopamine D₃ antagonist U-99194a maleate on locomotor activity and in a social interaction test in male mice was evaluated. Methods: Animals isolated during 30 days were treated with U-99194a maleate (20–40 mg/kg) or saline and locomotor activity was measured 20 min after drug administration. The behavioral interaction test was performed afterwards, between the experimental isolated animal and a standard opponent. Results: The higher dose used produces a significant decrease in spontaneous motor activity and presents an antiaggressive action without impairment of other behaviors, such as non-social exploration or immobility. At all doses tested, U-99194a maleate significantly increases social investigation. Conclusions: Our results give support to the hypothesis that the D₃ receptor could play a role in emotional behaviors. Received: 4 January 1999/Final version: 12 January 1999     

Topiramate increases the rewarding properties of cocaine in young-adult mice limiting its clinical usefulness

Rationale

Topiramate is an anticonvulsant drug which has been evaluated as a therapeutic option for the treatment of cocaine addiction during the last decade.

Objectives

The purpose of this study was to evaluate the effects of topiramate on the reinforcing actions of cocaine. To this aim, the topiramate-mediated regulation of acquisition and extinction phases of the cocaine conditioned place preference (CPP) was assessed in young-adult mice using three experimental designs.

Methods

Topiramate (50 mg/kg, p.o.) was given as follows: (1) during cocaine (1 and 25 mg/kg, i.p.) conditioning sessions (4 days) and cocaine (25 mg/kg) post-conditioning session; (2) 2 weeks before and during cocaine conditioning (25 mg/kg); and (3) during extinction of CPP induced by cocaine (25 mg/kg). In the first experimental design, changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) gene expressions were measured in the ventral tegmental area (VTA).

Results

Topiramate significantly increased cocaine-induced CPP and delayed or failed to produce extinction after the first cocaine reinstatement extinction in the first and second experiments. Furthermore, treatment with topiramate after place conditioning blocked the extinction of cocaine-induced CPP. TH and DAT gene expression in the VTA was significantly lower both with topiramate alone and in combination with cocaine compared with animals receiving only cocaine.

Conclusions

These findings suggest that topiramate increases the rewarding properties of cocaine, at least in part, by regulating dopaminergic signaling in the mesolimbic circuit. Consequently, the results of this study do not support the use of topiramate for the treatment of problems related to cocaine dependence.

Highlights

? Topiramate increases the rewarding properties of cocaine in CPP? Topiramate alters dopaminergic signaling in the mesolimbic circuit? Topiramate delays the extinction of cocaine-induced CPP? TH and DAT gene expression in the VTA decreases with topiramate and/or with cocaine? Results show that it should limit the use of topiramate in cocaine-dependent subjects

     

Assessment of Body Composition as an Indicator of Early Peripheral Parenteral Nutrition Therapy in Patients Undergoing Colorectal Cancer Surgery in an Enhanced Recovery Program

Background: A poor body composition (BC) has been identified as a risk factor for patients with colorectal cancer (CRC). This study was performed to assess the effect of early peripheral parenteral nutrition (PPN) on BC in patients undergoing CCR surgery within an enhanced recovery program. Methods: Patients with normal nutritional status were prospectively included between October 2016 and September 2019, randomized into two groups (PPN with periOlimel N4-E versus conventional fluid therapy) and subsequently classified according to their preoperative CT scan into high- or low-risk BC groups. Postoperative complications and length of hospital stay (LOS) were assessed. Results: Of the 156 patients analyzed, 88 patients (56.4%) were classified as having high-risk BC according to CT measurements. PPN led to a 15.4% reduction in postoperative complications in high-risk vs. 1.7% in low-risk BC patients. In the multivariate analysis, high-risk BC was related to an OR (95% CI) of 2 (p = 0.044) of presenting complications and of 1.9 (p = 0.066) for major complications, and was associated with an increase in LOS of 3.6 days (p = 0.039). Conclusions: The measurement of patients’ BC can allow for the identification of target patients where PPN has been proven to be an effective tool to improve postoperative outcomes.     

Effect of adolescent exposure to MDMA and cocaine on acquisition and reinstatement of morphine-induce CPP

It is well known that an elevated percentage of ecstasy users also consume cocaine. Recently, it has been reported that a high frequency of heroin smokers first consumed heroin under the effects of ecstasy with the hope of reducing the stimulant effects of the latter drug. The aim of the present study was to evaluate the effect of exposure to MDMA and cocaine during adolescence on morphine-induced conditioned place preference (CPP) and reinstatement in adulthood. In the first experiment, adolescent mice were exposed to six injections of MDMA and three weeks later their response to the reinforcing properties of 40 mg/kg of morphine was evaluated using the CPP paradigm. All the treatment groups developed the same magnitude of morphine-induced preference and, after CPP was extinguished, it was restored in all the groups with a priming dose of 10 mg/kg of morphine. Only mice that had been treated with 10 or 20 mg/kg of MDMA had their morphine-induced preference reinstated after receiving only 5 mg/kg of morphine. In the second experiment, adolescent mice were similarly treated with six administrations of cocaine (25 mg/kg) or cocaine plus MDMA (5, 10 or 20 mg/kg), and their response to morphine-induce CPP was evaluated three weeks later. Similarly to the first experiment, all the groups developed a preference for the morphine-paired compartment, but this preference was not reinstated with a priming dose of 10 mg/kg of morphine following extinction, as was the case among the control animals. These results lead us to hypothesize that periadolescent MDMA exposure alters responsiveness to the rewarding properties of morphine, highlighting MDMA as a gateway drug whose use may increase the likelihood of dependence on other drugs.     

Cannabinoid agonist-induced sensitisation to morphine place preference in mice

The influence of the endocannabinoid system on the sensitisation to the rewarding effects of morphine in the place conditioning paradigm was evaluated. In mice pretreated with morphine this drug induces place preference with lower doses. Pretreatment with non-rewarding doses of the cannabinoid agonist WIN 55,212-2 (0.5 and 1 mg/kg) induces sensitisation to the rewarding effects of morphine. However, the pretreatment with the cannabinoid antagonist SR 144716A plus morphine or WIN 55,212-2 blocks it. Our results suggest the existence of cross-talk between cannabinoids and opiates on the sensitisation to morphine and the implication of the endocannabinoid system in the process of sensitisation to opiates.     

A preliminary report on multiple family discussion groups for patients with chronic medical illness and its repercussions in the management of the hemodialysis process

The hemodialysis (HD) process involves an important degree of stress, not only for the patient but also for the family. The available data suggest that the quality of the family's performance predicts the degree of commitment that the patient acquires with the dialysis center. The establishment of a program of multiple family discussion groups allows exploration of the effect of the treatment on the patient in their context, not only regarding the illness, but also regarding the quality of life related to health, satisfaction and functional state. After the startup in the Hospital Virxe da Xunqueira of the multiple family discussion group (MFDG) for patients with chronic medical illness, the objective of this work was to evaluate the repercussions of the MFDG over the therapeutic fulfillment, the quality of life and the expectations of the patients in the chronic HD program, through the assessment of these indicators before and after their participation in this group. The MFDG was performed for a total of eight people, the families of four patients in the chronic HD program. Six weekly 1.5 hour sessions were performed and structured according to the following general contents: chronic illness impact component (2 sessions), family development component (3 sessions) and family illness integration component (1 session). Although no objectives were made for changes in relation to the therapeutic fulfillment, the average auto-effectiveness, locus of control, success and family general expectations went up slightly after the participation in the MFDG. The average specific self-effectiveness and family expectations in the presence of the illness reflected a modest increase, while the specific expectations of control locus and success in the presence of the illness decreased slightly. The scores obtained regarding the general state of health reflected a small decrease, while the evaluation of the quality of life of patients and family members showed a slight increase. We can conclude in the first place highlighting the viability of the MFDG, since no impediments were found either in recruitment of the families of the participants, or in preventing their excellent participation in the beginning and through the course of the group. Although no objectives were made for changes in relation to the therapeutic fulfillment, the high indices of satisfaction which the group obtained indicate that the discussion group is useful for the patients to find more support from their families, to change their view of the illness, to learn from other families new ways to resolve the difficulties and to increase their perception of capacity in the presence of the illness. The obtained data are preliminary and derived from only four families, but are encouraging as far as the improvement in the quality of life and the adjustment of the participants to the illness. Studies with the inclusion of more families are still pending in order to be able to arrive at conclusions based on a greater empiric basis. The records of MFDG for the families of HD patients are scarce. With this work it is attempted to reveal that these types of groups can be applied with these patients and their families, and they seem to prove beneficial for all those involved: patients, family and health professionals.     

Effects of dopamine antagonists with different receptor blockade profiles on morphine-induced place preference in male mice

The effects of dopamine (DA) antagonists with different selectivity for the DA receptors (SCH 23390, 0.5, 0.25, 0.125 mg/kg; haloperidol, 0.2, 0.1 mg/kg; raclopride, 1.2, 0.6, 0.3 mg/kg; risperidone, 0.4, 0.2, 0.1 mg/kg; U-99194A maleate, 40, 20 mg/kg; clozapine, 2.5, 1.25, 0.625 mg/kg) on the acquisition of place conditioning and morphine-induced conditioned place preference (CPP) were explored in male mice. Morphine (40 mg/kg) produced CPP while SCH 23390, haloperidol and clozapine (highest dose) and risperidone (lowest dose) produced conditioned place aversion (CPA). Raclopride and U-99194A maleate did not produce CPP or CPA. Morphine-induced CPP was reversed by the administration of SCH 23390 and risperidone (all doses), haloperidol (highest dose) and raclopride and clozapine (intermediate and lowest doses). U-99194A maleate did not reverse morphine-induced CPP. These results suggest that the conditioned rewarding effects of morphine are mediated by the different subtypes of DA receptors.