Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effect of the intrategmental infusions on extracellular dopamine in the ipsilateral nucleus accumbens were recorded with a second microdialysis probe. Intrategmental infusion of muscimol (10-40 microM) or baclofen (50 microM) decreased extracellular dopamine in the nucleus accumbens. Intrategmental infusion of NMDA (1 mM, 15 min) or kainate (50 microM, 15 min) increased extracellular dopamine in the nucleus accumbens. The effects of the excitatory amino acids were suppressed by co-infusion of MK-801 (1 MM), (+)-3-amino-1-hydroxy-2-pyrrolidone [(+)-HA966; 1 mM], (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX;300 microM). Intrategmental infusion of of carbachol (50 microM) increased extracellular dopamine in the nucleus accumbens. These results provide evidence for localization of GABAA, GABAB NMDA, non-NMDA, and cholinergic receptors on dopamine neurons in the VTA. Infusions of CPP, (+)-MK-801, (+)-HA966, CNQX, mecamylamine, atropine, or 3-[[(3,4-dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid (CGP 52432) into the VTA did not modify extracellular dopamine in the nucleus accumbens. Infusion of bicuculline (50 microM) and (-)-sulpiride (50 microM) was followed by an increase in extracellular dopamine in the nucleus accumbens. These data suggest that dopamine neurons in the VTA are tonically inhibited by GABA and dopamine by acting on GABAA, and D2 receptors, respectively. A tonic stimulation by glutamatergic or cholinergic neurons was not detected. Finally, results on A10 neurons are compared with earlier data on A9 neurons. A striking difference was found in that GABAA-dopamine interactions are indirect in the substantia nigra and direct in the VTA.

Background Clinical medication reviews (CMRs) are increasingly performed in older persons with multimorbidity and polypharmacy to reduce drug-related problems (DRPs). However, there is limited evidence that a CMR can improve clinical outcomes. Little attention has been paid to patients’ preferences and needs. The aim of this study was to investigate the effect of a patient-centred CMR, focused on personal goals, on health-related quality of life (HR-QoL), and on number of health problems. Methods and findings This study was a randomised controlled trial (RCT) performed in 35 community pharmacies and cooperating general practices in the Netherlands. Community-dwelling older persons (≥70 years) with polypharmacy (≥7 long-term medications) were randomly assigned to usual care or to receive a CMR. Randomisation was performed at the patient level per pharmacy using block randomisation. The primary outcomes were HR-QoL (assessed with EuroQol [EQ]-5D-5L and EQ-Visual Analogue Scale [VAS]) and number of health problems (such as pain or dizziness), after 3 and 6 months. Health problems were measured with a self-developed written questionnaire as the total number of health problems and number of health problems with a moderate to severe impact on daily life. Between April 2016 and February 2017, we recruited 629 participants (54% females, median age 79 years) and randomly assigned them to receive the intervention ( n = 315) or usual care ( n = 314). Over 6 months, in the intervention group, HR-QoL measured with EQ-VAS increased by 3.4 points (95% confidence interval [CI] 0.94 to 5.8; p = 0.006), and the number of health problems with impact on daily life decreased by 12% (difference at 6 months −0.34; 95% CI −0.62 to −0.044; p = 0.024) as compared with the control group. There was no significant difference between the intervention group and control group for HR-QoL measured with EQ-5D-5L (difference at 6 months = −0.0022; 95% CI −0.024 to 0.020; p = 0.85) or total number of health problems (difference at 6 months = −0.30; 95% CI −0.64 to 0.054; p = 0.099). The main study limitations include the risk of bias due to the lack of blinding and difficulties in demonstrating which part of this complex intervention (for example, goal setting, extra attention to patients, reducing health problems, drug changes) contributed to the effects that we observed. Conclusions In this study, we observed that a CMR focused on personal goals improved older patients’ lives and wellbeing by increasing quality of life measured with EQ-VAS and decreasing the number of health problems with impact on daily life, although it did not significantly affect quality of life measured with the EQ-5D. Including the patient’s personal goals and preferences in a medication review may help to establish these effects on outcome...

This study shows that patients using automated drug dispensing have a high number of DRPs. Medication review decreases the number of DRPs among these patients. We recommend that all patients with automatic drug dispensing should have a thorough medication review by pharmacists and prescribers.

This systematic review shows a significant association between the number of key elements of the intervention reflecting collaborative aspects in medication review and the implementation rate of recommendations.