Daily Optogenetic Stimulation of the Left Infralimbic Cortex Reverses Extinction Impairments in Male Rats Exposed to Single Prolonged Stress.

Post-traumatic stress disorder (PTSD) is associated with decreased activity in the prefrontal cortex. PTSD-like pathophysiology and behaviors have been observed in rodents exposed to a single prolonged stress (SPS) procedure. When animals are left alone for 7 days after SPS treatment, they show increased anxiety-like behavior and impaired extinction of conditioned fear, and reduced activity in the prefrontal cortex. Here, we tested the hypothesis that daily optogenetic stimulation of the infralimbic region (IL) of the medial prefrontal cortex (mPFC) during the 7 days after SPS would reverse SPS effects on anxiety and fear extinction. Male Sprague-Dawley rats underwent SPS and then received daily optogenetic stimulation (20 Hz, 2 s trains, every 10 s for 15 min/day) of glutamatergic neurons of the left or right IL for seven days. After this incubation period, rats were tested in the elevated plus-maze (EPM). Twenty-four hours after the EPM test, rats underwent auditory fear conditioning (AFC), extinction training and a retention test. SPS increased anxiety-like behavior in the EPM task and produced a profound impairment in extinction of AFC. Optogenetic stimulation of the left IL, but not right, during the 7-day incubation period reversed the extinction impairment. Optogenetic stimulation did not reverse the increased anxiety-like behavior, suggesting that the extinction effects are not due to a treatment-induced reduction in anxiety. Results indicate that increased activity of the left IL after traumatic experiences can prevent development of extinction impairments. These findings suggest that non-invasive brain stimulation may be a useful tool for preventing maladaptive responses to trauma.

Effects of Ethanol Exposure During Adolescence or Adulthood on Locomotor Sensitization and Dopamine Levels in the Reward System.

Behavioral sensitization is a process of neuroadaptation characterized by a gradual increase in motor behaviors. The major neural substrates involved in the behavioral sensitization lie on the dopaminergic mesocorticolimbic pathway, which is still under development during adolescence. To investigate age-differences in ethanol behavioral sensitization and dopamine levels in distinct brain regions of the reward system, adolescent and adult mice were repeatedly pretreated with saline or ethanol (2.0 g/kg i.p.) during 15 consecutive days and challenged with saline or ethanol 5 days after pretreatment. Dopamine and its metabolites were measured in tissue samples of the prefrontal cortex (PFC), nucleus accumbens (NAc) and striatum by HPLC analysis. While repeated ethanol administration resulted in the development of locomotor sensitization in both adult and adolescent mice, only the adults expressed sensitization to a subsequent ethanol challenge injection. Neurochemical results showed reduced dopamine levels in adolescents compared to adults. Specifically, mice pretreated with ethanol during adolescence displayed lower dopamine levels in the PFC compared to the respective adult group in response to an ethanol challenge injection, and preadolescent mice exhibited lower dopamine levels in the NAc following an acute ethanol treatment compared to adults. These findings suggest that adolescent mice are not only less sensitive to the expression of ethanol-induced sensitization than adults, but also show lower dopamine content after ethanol exposition in the PFC and NAc.

Safety assessment of potentially inappropriate medications use in older people and the factors associated with hospital admission.

PURPOSE: Potentially Inappropriate Medications (PIM) use in elderly people may be responsible for the development of Adverse Drug Reaction (ADR) which, when severe, leads to hospital admissions. OBJECTIVES: to estimate the prevalence of elderly who had used PIM before being admitted to hospital admission and to identify the risk factors and the hospitalizations related to ADR arising from PIM. METHODS: A descriptive and cross-sectional study was performed in the internal medicine ward of a teaching hospital (Brazil), in 2008. With the aid of a validated form, patients aged ≥ 60 years, with length of hospital stay ≥ 24 hours, were interviewed about drugs taken prior to the hospital admission and the complaints/reasons for hospitalization. RESULTS: 19.1% (59/308) of older patients had taken PIM before hospital admission and in 4.9%; there were a causal relation between the PIM taken and the complaint reported. PIM responsible for admissions were: amiodarone, amitriptyline, cimetidine, clonidine, diazepam, digoxin, estrogen, fluoxetine, lorazepam, short-acting nifedipine and propranolol. 47.0% of the clinical manifestations of PIM-related ADR were: dizziness, fatigue, digoxin toxicity and erythema. Only polypharmacy was detected as a risk factor for the occurrence of ADR of PIM (p = 0.02). CONCLUSION: PIM use in elderly people is not a risk factor for ADR-related hospital admission. Probably, severe ADR, which lead to hospitalizations of older people, can be explained by idiosyncratic response or the predisposition of these patients to develop adverse drug events, whether or not drugs are classed as PIM.

Effect of chronic treatment with clomipramine on food intake, macronutrient selection and body weight gain in rats.

Long-term treatment with clomipramine (CMI), a tricyclic antidepressant, induces food craving and body weight gain in patients. The present study investigated the effects of chronic treatment with CMI on total food intake, macronutrient selection, and body weight gain in rats. Male Wistar rats were maintained on a dietary self-selection regime with separate sources of protein, fat and carbohydrate. Animals received i.p. injections of CMI (0, 3, 10, 30 mg/kg) during 27 consecutive days. Food consumption and body weight were recorded daily and results were calculated as average of three consecutive days, namely during pre-treatment (3 d before pharmacological treatment), treatment (7th-9th; 16th-18th and 25th-27th days), and post-treatment (28th-33rd days). Results showed that CMI (30 mg/kg) significantly decreased energy intake during all treatment period, an effect that was related to a decrease in both carbohydrate-rich diet intake and body weight gain. At dose of 3 mg/kg CMI increased the total energy intake in the 16th-18th days, suggesting an apparent biphasic effect of chronic treatment with CMI on caloric intake. Chronic administration with CMI (27 d) did not alter protein-rich or fat-rich diet consumption. The main result of this study indicated that chronic treatment with CMI decreases rather than increase food consumption and body weight gain in rats exposed to a macronutrient self-selection procedure.