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1.
Neuropharmacology ; 180: 108290, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32888961

RESUMEN

Relapse into drug use is a significant problem for people recovering from addiction. The ability that conditioned cues have to reinstate and reinvigorate drug-seeking is potentiated over time (incubation of seeking), posing an additional difficulty for maintaining abstinence. While the prefrontal cortex has been involved in the incubation phenomenon and the extracellular matrix, perineuronal nets (PNNs) in particular, may play a vital role in brain plasticity associated to drug relapse, there are no comparative analyses between different drug classes and natural reinforcers. Here, we compare the effects of early (1 day) and protracted (30 days) withdrawal from to cocaine, heroin and sucrose self-administration on the total density and density per intensity range of PNNs of different territories of the prefrontal cortex of male Lewis rats. Our results show that cocaine self-administration increases the density of PNNs in the dorsal prelimbic, infralimbic and ventral orbitofrontal cortices, while protracted withdrawal reversesthis effect in the dorsal prelimbic cortex. Also, heroin self-administration increases the density of PNNs in the infralimbic cortex and ventral orbitofrontal cortices, but this effect is lost after 30 days of withdrawal in the infralimbic cortex. Finally, the self-administration of sucrose-sweetened water or the protracted withdrawal from this powerful reinforcer does not affect any of the PNN parameters analysed. Our results show that two different drugs of abuse (but not a natural reward) with specific pharmacological and physiological actions, differentially modulate PNNs in specific areas of the rodent prefrontal cortex with potential implications for the incubation of seeking phenomenon.


Asunto(s)
Cocaína/administración & dosificación , Heroína/administración & dosificación , Red Nerviosa/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Sacarosa/administración & dosificación , Analgésicos Opioides/administración & dosificación , Animales , Inhibidores de Captación de Dopamina/administración & dosificación , Masculino , Red Nerviosa/metabolismo , Nervios Periféricos/metabolismo , Corteza Prefrontal/metabolismo , Ratas , Ratas Endogámicas Lew , Autoadministración
2.
Artículo en Inglés | MEDLINE | ID: mdl-29100975

RESUMEN

BACKGROUND: Neurosurgeries such as gamma ventral capsulotomy (GVC) are an option for otherwise intractable obsessive-compulsive disorder (OCD) patients. In general, clinical and neuropsychological status both improve after GVC. However, its consequences on personality traits are not well-studied. The objective of this study was to investigate personality changes after one year of GVC in intractable OCD patients. METHODS: The personality assessment was conducted using the Revised NEO Personality Inventory (NEO PI-R) and Cloninger's Temperament and Character Inventory (TCI) in 14 intractable OCD patients before and one year after GVC. Comparisons of personality features between treatment responders (n=5) and non-responders (n=9) were performed. Multiple linear regression was also used for predicting changes in clinical and global functioning variables. RESULTS: Overall, no deleterious effect was found in personality after GVC. Responders had a reduction in neuroticism (p=0.043) and an increase in extraversion (p=0.043). No significant changes were observed in non-responders. Increases in novelty seeking and self-directedness, and decreases in persistence and cooperativiness predicted OCD symptom improvement. Similary, improvement in functioning was also predicted by hgher novelty seeking and self-directedness after GVC, whereas better functioning was also associated with lower reward dependence and cooperativeness after surgery. CONCLUSIONS: The pattern of changes in personality traits after GVC was generally towards that observed in nonclinical population, and does not raise safety concerns.


Asunto(s)
Trastorno Obsesivo Compulsivo/psicología , Trastorno Obsesivo Compulsivo/terapia , Personalidad , Adulto , Femenino , Estudios de Seguimiento , Humanos , Cápsula Interna/efectos de la radiación , Modelos Lineales , Masculino , Inventario de Personalidad , Escalas de Valoración Psiquiátrica , Radiocirugia , Resultado del Tratamiento
3.
JAMA Netw Open ; 1(7): e185275, 2018 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-30646396

RESUMEN

Importance: Deep brain stimulation (DBS) has been investigated for treatment of morbid obesity with variable results. Patients with Prader-Willi syndrome (PWS) present with obesity that is often difficult to treat. Objective: To test the safety and study the outcome of DBS in patients with PWS. Design, Setting, and Participants: This case series was conducted in the Hospital das Clínicas, University of São Paulo, Brazil. Four patients with genetically confirmed PWS presenting with severe obesity were included. Exposure: Deep brain stimulation electrodes were bilaterally implanted in the lateral hypothalamic area. After DBS implantation, the treatment included the following phases: titration (1-2 months), stimulation off (2 months), low-frequency DBS (40 Hz; 1 month), washout (15 days), high-frequency DBS (130 Hz; 1 month), and long-term follow-up (6 months). Main Outcomes and Measures: Primary outcome measures were adverse events recorded during stimulation and long-term DBS treatment. Secondary outcomes consisted of changes in anthropometric measures (weight, body mass index [calculated as weight in kilograms divided by height in meters squared], and abdominal and neck circumference), bioimpedanciometry, and calorimetry after 6 months of treatment compared with baseline. The following evaluations and measurements were conducted before and after DBS: clinical, neurological, psychiatric, neuropsychological, anthropometry, calorimetry, blood workup, hormonal levels, and sleep studies. Adverse effects were monitored during all follow-up visits. Results: Four patients with PWS were included (2 male and 2 female; ages 18-28 years). Baseline mean (SD) body mass index was 39.6 (11.1). Two patients had previous bariatric surgery, and all presented with psychiatric comorbidity, which was well controlled with the use of medications. At 6 months after long-term DBS, patients had a mean 9.6% increase in weight, 5.8% increase in body mass index, 8.4% increase in abdominal circumference, 4.2% increase in neck circumference, 5.3% increase in the percentage of body fat, and 0% change in calorimetry compared with baseline. Also unchanged were hormonal levels and results of blood workup, sleep studies, and neuropsychological evaluations. Two patients developed stimulation-induced manic symptoms. Discontinuation of DBS controlled this symptom in 1 patient. The other required adjustments in medication dosage. Two infections were documented, 1 associated with skin picking. Conclusions and Relevance: Safety of lateral hypothalamic area stimulation was in the range of that demonstrated in patients with similar psychiatric conditions receiving DBS. In the small cohort of patients with PWS treated in our study, DBS was largely ineffective.


Asunto(s)
Estimulación Encefálica Profunda , Hipotálamo/cirugía , Obesidad Mórbida/etiología , Obesidad Mórbida/cirugía , Síndrome de Prader-Willi/complicaciones , Adolescente , Adulto , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Femenino , Humanos , Masculino , Adulto Joven
4.
Ann Clin Transl Neurol ; 4(12): 897-901, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29296618

RESUMEN

Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader-Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alpha-frequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity.

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