High cocaine dosage decreases neurogenesis in the hippocampus and impairs working memory.

Drug addiction is a chronic brain disorder, characterized by the loss of the ability to control drug consumption. The neurobiology of addiction is traditionally thought to involve the mesocorticolimbic system of the brain. However, the hippocampus has received renewed interest for its potential role in addiction. Part of this attention is because of the fact that drugs of abuse are potent negative regulators of neurogenesis in the adult hippocampus and may as a result impair learning and memory. We investigated the effects of different dosages of contingent cocaine on cell proliferation and neurogenesis in the dentate gyrus of the hippocampus and on working memory during abstinence, using the water T-maze test, in adult rats. We found that cocaine, in addition to the changes it produces in the reward system, if taken in high doses, can attenuate the production and development of new neurons in the hippocampus, and reduce working memory.

Antidepressant treatment facilitates dopamine release and drug seeking behavior in a genetic animal model of depression.

Anhedonia and lack of motivation are core symptoms of depression. In contrast, hyper-motivation and euphoria characterize intoxicated states. In order to explore the relationship between these two behavioral states we examined cocaine self-administration tasks in an animal model of depression [Flinders Sensitive Line (FSL) rats]. We found that FSL rats exhibit sub-sensitivity in their cocaine-seeking behavior, which was normalized following a chronic treatment with the antidepressant desipramine. However, when the cocaine dosage was increased, FSL rats demonstrated a similar cocaine-seeking behavior to that of controls. In light of dopamine's central role in modulating cocaine reinforcement, we examined dopaminergic neurotransmission in the nucleus accumbens, a brain region implicated in the rewarding and hedonic effects of substances of misuse. FSL rats exhibited low but dose-dependent increases in extracellular levels of dopamine in the nucleus accumbens after acute intravenous cocaine injection. Furthermore, by using the dopamine transporter blocker GBR-12909 we were able to demonstrate that the low extracellular dopamine levels, observed in FSL rats, were a consequence of low dopamine release in the nucleus accumbens, as opposed to the possibility of increased uptake. Treatment of FSL rats with the antidepressant desipramine raised cocaine- and GBR-12909-induced dopamine release to the level of controls. This treatment also resulted in increased cocaine-seeking behavior.

Personal health records, global policy and regulation review.

Personal health records (PHR) have been endorsed as a promising tool for the self-management of an individual's medical information, affording benefits to both the individual patient and the healthcare system as a whole. Nevertheless, adoption rates have been relatively slow and widespread acceptance has yet to be achieved. A significant obstacle often cited as delaying the implementation of these systems has been concern regarding the ability to properly ensure the security and privacy of this sensitive information. This article reviews the current legislative landscape in various countries, examining the degree to which they address these issues and support the implementation of PHR's. This review compares in particular a number of prominent components of health data security and privacy across five different legislative jurisdictions in order to allow for a closer examination of regulatory approaches and measures. Of the legislation reviewed the EU's GDPR stands out as seemingly providing the most comprehensive and stringent protection measures, yet nonetheless appears to leave significant room for interpretation and a degree of ambiguity in key areas. The results of this comparison, demonstrate considerable variances with regards to legal terminology and the degree of compliance required from entities offering PHR services across various jurisdictions. The paper ends with a discussion of specific policy implications and recommendations stemming from the current legislative state of affairs.

Monitoring of circadian rhythms of heart rate, locomotor activity, and temperature for diagnosis and evaluation of response to treatment in an animal model of depression.

Depressive disorders affect approximately 5% of the population in developed countries each year. Current antidepressant treatment usually requires several weeks to obtain response or remission and is only effective in about half of depressed patients. Objective diagnostic tools and detection of symptom relief by physiological biomarkers may assist in the clinical decision-making process regarding the selection, replacing, and augmenting of antidepressants. Furthermore, such biomarkers may enable early prediction of the appropriateness of a specific antidepressant for a particular patient. Here, we examined a new non-invasive method for objective diagnosis of depressive-like behavior and for the purpose of predicting antidepressant (paroxetine and desipramine) treatment effectiveness. This method employed a genetic rat model of depression and mathematical analysis of physiological parameters, of circadian rhythms of heart rate, locomotor activity, and temperature for diagnosis and evaluation of response to treatment in an animal model of depression. By utilizing this method, we were able to discern, in a rat model, between depressive and non-depressive individuals and to predict beneficial response to the antidepressants. Mathematical analysis of physiological parameters such as heart rate, locomotor activity, and temperature circadian rhythms can be used for objective diagnosis of depressive-like behavior and for early prediction of response to antidepressant treatment.

Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration.

The lateral habenula (LHb) plays a role in prediction of negative reinforcement, punishment and aversive responses. In the current study, we examined the role that the LHb plays in regulation of negative reward responses and aversion. First, we tested the effect of intervention in LHb activity on sucrose reinforcing behavior. An electrode was implanted into the LHb and rats were trained to self-administer sucrose (20%; 16 days) until at least three days of stable performance were achieved (as represented by the number of active lever presses in self-administration cages). Rats subsequently received deep brain stimulation (DBS) of the LHb, which significantly reduced sucrose self-administration levels. In contrast, lesion of the LHb increased sucrose-seeking behavior, as demonstrated by a delayed extinction response to substitution of sucrose with water. Furthermore, in a modified non-rewarding conditioned-place-preference paradigm, DBS of the LHb led to aversion to the context associated with stimulation of this brain region. We postulate that electrical stimulation of the LHb attenuates positive reward-associated reinforcement by natural substances.

Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior.

The lateral habenula (LHb) is critical for modulation of negative reinforcement, punishment and aversive responses. In light of the success of deep-brain-stimulation (DBS) in the treatment of neurological disorders, we explored the use of LHb DBS as a method of intervention in cocaine self-administration, extinction, and reinstatement in rats. An electrode was implanted into the LHb and rats were trained to self-administer cocaine (21 days; 0.25-1 mg/kg) until they achieved at least three days of stable performance (as measured by daily recordings of active lever presses in self-administration cages). Thereafter, rats received DBS in the presence or absence of cocaine. DBS reduced cocaine seeking behavior during both self-administration and extinction training. DBS also attenuated the rats' lever presses following cocaine reinstatement (5-20 mg/kg) in comparison to sham-operated rats. These results were also controlled by the assessment of physical performance as measured by water self-administration and an open field test, and by evaluation of depressive-like manifestations as measured by the swim and two-bottles-choice tests. In contrast, LHb lesioned rats demonstrated increased cocaine seeking behavior as demonstrated by a delayed extinction response. In the ventral tegmental area, cocaine self-administration elevated glutamatergic receptor subunits NR1 and GluR1 and scaffolding protein PSD95, but not GABA(A)ß, protein levels. Following DBS treatment, levels of these subunits returned to control values. We postulate that the effect of both LHb modulation and LHb DBS on cocaine reinforcement may be via attenuation of the cocaine-induced increase in glutaminergic input to the VTA.

Programmed acute electrical stimulation of ventral tegmental area alleviates depressive-like behavior.

Depressive disorders affect approximately 5% of the population in any given year. Antidepressants may require several weeks to produce their clinical effects. Despite progress being made in this area there is still room and a need to explore additional therapeutic modes to increase treatment effectiveness and responsiveness. Herein, we examined a new method for intervention in depressive states based on deep brain stimulation of the ventral tegmental area (VTA) as a source of incentive motivation and hedonia, in comparison to chemical antidepressants. The pattern of stimulation was fashioned to mimic the firing pattern of VTA neurons in the normal rat. Behavioral manifestations of depression were then monitored weekly using a battery of behavioral tests. The results suggest that treatment with programmed acute electrical stimulation of the VTA substantially alleviates depressive behavior, as compared to chemical antidepressants or electroconvulsive therapy, both in onset time and longitudinal effect. These results were also highly correlated with increases in brain-derived neurotrophic factor mRNA levels in the prefrontal cortex.