Development and validation of the dizziness fear-avoidance behaviours and beliefs inventory for patients with vestibular disorders.

The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Dizziness Fear-Avoidance Behaviours and Beliefs Inventory (D-FABBI)) designed to measure fear-avoidance behaviors and cognitions related to dizziness disability. A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability, and convergent/discriminant validity) a new instrument. A total of 198 patients with vestibular disorders (acute vestibular syndrome (AVS), 23.2%; chronic vestibular syndrome (CVS), 35.4%; and episodic vestibular syndrome (EVS) 41.4%) were recruited. Sociodemographic characteristics, the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) and D-FABBI were evaluated. The final version of the D-FABBI consists of 17 items distributed across two subscales: activities of daily living fear-avoidance and movement fear-avoidance. The D-FABBI showed high internal consistency (Cronbach α = 0.932; 95% CI [0.91-0.94]) and so did the subscales (Cronbach α > 0.8). The exploratory structural equation model and confirmatory factor analysis provided better fit results, with a comparative fit index and root mean square error of approximation values of 0.907 to 0.081. No floor or ceiling effects were identified. There was a positive, significant, and moderate-strong magnitude correlation with the total DHI (r = 0.62) and low-moderate with respect to the HADS depression (r = 0.35) and HADS anxiety subscales (r = 0.26). The patients with CVS had a higher D-FABBI score than those with AVS or EVS. The D-FABBI appears to be a valid and reliable instrument for measuring the fear-avoidance behaviors and cognition related to dizziness disability of patients with vestibular disorders.

Mental Disorder Diagnosis from EEG Signals Employing Automated Leaning Procedures Based on Radial Basis Functions.

Purpose: In this paper, a new automated procedure based on deep learning methods for schizophrenia diagnosis is presented. Methods: To this aim, electroencephalogram signals obtained using a 32-channel helmet are prominently used to analyze high temporal resolution information from the brain. By these means, the data collected is employed to evaluate the class likelihoods using a neuronal network based on radial basis functions and a fuzzy means algorithm. Results: The results obtained with real datasets validate the high accuracy of the proposed classification method. Thus, effectively characterizing the changes in EEG signals acquired from schizophrenia patients and healthy volunteers. More specifically, values of accuracy better than 93% has been obtained in the present research. Additionally, a comparative study with other approaches based on well-knows machine learning methods shows that the proposed method provides better results than recently proposed algorithms in schizophrenia detection. Conclusion: The proposed method can be used as a diagnostic tool in the detection of the schizophrenia, helping for early diagnosis and treatment.

Maternal separation increases cocaine intake through a mechanism involving plasticity in glutamate signalling.

Early-life stress (ELS) is associated with negative consequences, including maladaptive long-lasting brain effects. These alterations seem to increase the likelihood of developing substance use disorders. However, the molecular consequences of ELS are poorly understood. In the present study, we tested the impact of ELS induced by maternal separation with early weaning (MSEW) in CD1 male mice at different phases of cocaine self-administration (SA). We also investigated the subsequent alterations on GluR2, GluR1, cAMP response element-binding (CREB), and CREB-phosphorylation (pCREB) in ventral tegmental area (VTA) and nucleus accumbens (NAc) induced by both MSEW and cocaine SA. Our results show that MSEW animals expressed a higher cocaine intake, an increased vulnerability to the acquisition of cocaine SA, and incapacity to extinguish cocaine SA behaviour. MSEW mice showed decreased GluR2 and increased GluR1 and pCREB in NAc. Also, results displayed reduction of basal levels of GluR1 and CREB and an elevation of GluR1/GluR2 ratio in the VTA. Such results hint at an enhanced glutamatergic function in NAc and increased excitability of VTA DA neurons in maternally separated mice. Altogether, our results suggest that MSEW induces molecular alterations in the brain areas related to reward processing, increasing the vulnerability to depression and cocaine-seeking behaviour.

The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake.

The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self-administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self-administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6-day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol-induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol-induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice.

BACKGROUND AND PURPOSE: Alcohol exposure in utero may lead to a wide range of long-lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long-term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward-related behaviours in adult offspring. EXPERIMENTAL APPROACH: Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking-in-the-dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine-induced motivational responses (conditioned place preference, behavioural sensitization and operant self-administration). Protein expression of dopamine- and glutamate-related molecules was assessed following cocaine-induced reinstatement. KEY RESULTS: The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine-paired chamber in the conditioned place preference test. Furthermore, early alcohol-exposed mice displayed attenuated cocaine-induced behavioural sensitization but also higher cocaine self-administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol-exposed mice after cocaine-primed reinstatement. CONCLUSION AND IMPLICATIONS: Our findings demonstrate that maternal binge-like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol-exposed offspring to develop drug addiction later in adulthood.

Oxytocin prevents the increase of cocaine-related responses produced by social defeat.

The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (RSD). During the social defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum and hippocampus was also measured. Our results confirm that raising the levels of OXT during social defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by social defeat and modifies BDNF levels in all the structures we have studied. Moreover, OXT prevents RSD-induced increases in the motivational effects of cocaine. Administration of OXT before each social defeat blocked the social defeat-induced increment in the conditioned rewarding effects of cocaine in the CPP, favored the extinction of cocaine-associated memories in both the CPP and SA, and decreased reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects.

Repeated Cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus.

Cannabinoid derivatives have shown promising results for treating neuropsychiatric disorders, including drug addiction. Recent studies on the therapeutic effects of Cannabidiol (CBD) on drug abuse showed mixed results, especially with psychostimulant substances such as cocaine. To determine whether CBD can attenuate cocaine reinforcement, we assessed behavioural responses induced by cocaine in mice, using the behavioural sensitization, conditioned place preference and intravenous self-administration paradigms. We show that repeated CBD treatment produces anxiolytic effects in the elevated plus maze test, increases the discrimination index of the novel object recognition task and attenuates cocaine-induced conditioned place preference but does not affect behavioural sensitization. CBD reduced cocaine voluntary consumption and progressive ratio breaking point in the self-administration paradigm, but not drug-induced reinstatement. In parallel, CBD increased expression of type 1 cannabinoid receptor, MAPK-CREB phosphorylation, BDNF expression, and neural cell proliferation in the hippocampus, and reduced the GluA1/2 AMPA subunit receptor ratio in the striatum. In summary, we show that CBD can modulate some behavioural and molecular manifestations of cocaine reinforcement. Moreover, our findings show that CBD has pro-neurogenic effects also in cocaine consuming animals. Overall, this novel evidence provides new perspectives to use CBD as a therapeutic tool.