Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats.

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we performed 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. Food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson's disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particular the intake of fat.

Ablation of the tail of the ventral tegmental area compensates symptoms in an experimental model of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder partly caused by the loss of the dopamine neurons of the nigrostriatal pathway. It is accompanied by motor as well as non-motor symptoms, including pain and depression. The tail of the ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) is a GABAergic mesopontine structure that acts as a major inhibitory brake for the substantia nigra pars compacta (SNc) dopamine cells, thus controlling their neuronal activity and related motor functions. The present study tested the influence of suppressing this tVTA brake on motor and non-motor symptoms in a rat model of Parkinson's disease. Using behavioral approaches, we showed that male Sprague-Dawley rats with bilateral and partial 6-hydroxydopamine SNc lesion displayed motor impairments in the rotarod test, impairments that were no more present following a co-lesion of the tVTA. Using a larger set of behavioral tests, we then showed that such SNc lesion also led to non-motor symptoms, including lower body weight, lower mechanical nociceptive thresholds in the forceps test and lower thermal nociceptive thresholds in the incremented hot-plate test, and a decreased sucrose preference in a 2-bottle choice paradigm. The excitotoxic co-lesion of the tVTA led to compensation of body weight, mechanical nociceptive thresholds and anhedonia-like behavior. These findings illustrate the major influence that the tVTA exerts on the dopamine system, modulating the motor and non-motor symptoms related to a partial loss of dopamine cells.

Morphine-dependent and abstinent mice are characterized by a broader distribution of the neurons co-expressing mu and delta opioid receptors.

Opiate addiction develops as a chronic relapsing disorder upon drug recreational use or following misuse of analgesic prescription. Mu opioid (MOP) receptors are the primary molecular target of opiates but increasing evidence support in vivo functional heteromerization with the delta opioid (DOP) receptor, which may be part of the neurobiological processes underlying opiate addiction. Here, we used double knock-in mice co-expressing fluorescent versions of the MOP and DOP receptors to examine the impact of chronic morphine administration on the distribution of neurons co-expressing the two receptors. Our data show that MOP/DOP neuronal co-expression is broader in morphine-dependent mice and is detected in novel brain areas located in circuits related to drug reward, motor activity, visceral control and emotional processing underlying withdrawal. After four weeks of abstinence, MOP/DOP neuronal co-expression is still detectable in a large number of these brain areas except in the motor circuit. Importantly, chronic morphine administration increased the proportion of MOP/DOP neurons in the brainstem of morphine-dependent and abstinent mice. These findings establish persistent changes in the abstinent state that may modulate relapse and opiate-induced hyperalgesia and also point to the therapeutic potential of MOP/DOP targeting. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.

The hidden side of Parkinson's disease: Studying pain, anxiety and depression in animal models.

Parkinson's disease is a neurodegenerative disease leading to the loss of midbrain dopamine neurons. It is well known and characterized by motor symptoms that are secondary to the loss of dopamine innervation, but it is also accompanied by a range of various non-motor symptoms, including pain and psychiatric disorders such as anxiety and depression. These non-motor symptoms usually appear at early stages of the disease, sometimes even before the first motor symptoms, and have a dramatic impact on the quality of life of the patients. We review here the present state-of-the-art concerning pain, anxiety and depression-like parameters in animal models of Parkinson's disease.

Response of the Tail of the Ventral Tegmental Area to Aversive Stimuli.

The GABAergic tail of the ventral tegmental area (tVTA), also named rostromedial tegmental nucleus (RMTg), exerts an inhibitory control on dopamine neurons of the VTA and substantia nigra. The tVTA has been implicated in avoidance behaviors, response to drugs of abuse, reward prediction error, and motor functions. Stimulation of the lateral habenula (LHb) inputs to the tVTA, or of the tVTA itself, induces avoidance behaviors, which suggests a role of the tVTA in processing aversive information. Our aim was to test the impact of aversive stimuli on the molecular recruitment of the tVTA, and the behavioral consequences of tVTA lesions. In rats, we assessed Fos response to lithium chloride (LiCl), ß-carboline, naloxone, lipopolysaccharide (LPS), inflammatory pain, neuropathic pain, foot-shock, restraint stress, forced swimming, predator odor, and opiate withdrawal. We also determined the effect of tVTA bilateral ablation on physical signs of opiate withdrawal, and on LPS- and LiCl-induced conditioned taste aversion (CTA). Naloxone-precipitated opiate withdrawal induced Fos in µ-opioid receptor-positive (15%) and -negative (85%) tVTA cells, suggesting the presence of both direct and indirect mechanisms in tVTA recruitment during withdrawal. However, tVTA lesion did not impact physical signs of opiate withdrawal. Fos induction was also present with repeated, but not single, foot-shock delivery. However, such induction was mostly absent with other aversive stimuli. Moreover, tVTA ablation had no impact on CTA. Although stimulation of the tVTA favors avoidance behaviors, present findings suggest that this structure may be important to the response to some, but not all, aversive stimuli.

[Palliative care practices in residential facilities for the elderly requiring full-time care]. / Les pratiques des soins palliatifs en établissement d’hébergement pour personnes âgées dépendantes.

AIMS: The purpose of this study was to assess palliative care practices for residents of Larmont residential facilities for the elderly requiring full-time care (Doubs, France) throughout their stay. METHODS: This was a healthcare peer review based on a retrospective clinical audit in compliance with the recommendations of the French Health Authority. The 252-bed Larmont residential care facilities for the elderly is a public institution, attached to the local Hospital. The 72 residents of the Larmont residential care facilities for the elderly who died during 2012 were included in the study. RESULTS: Death occurred on the premises for 95.8 percent of residents. The proposal to appoint a support person was recorded in 27.6 percent of audited cases. End-of-life instructions were recorded in 23.2 percent of cases. In 31.8 percent of cases, the medical record referred to a multidisciplinary procedure, which complied with regulations in less than one half of cases. The residents' pain at the end of their life was insufficiently assessed and managed. A discomfort other than pain was identified in 89.2 percent of cases. CONCLUSIONS: This healthcare peer review led to a quality improvement plan focusing on three areas : ensure that medical practices are in line with patients' rights, anticipate identification of the end of life and improve management of pain and suffering at the end of life.