Apathy and impulsiveness in Parkinson disease: Two faces of the same coin?

Apathy and impulsiveness are 2 common non-motor symptoms in Parkinson disease that could occur in different periods or simultaneously. Apathy and impulsiveness could be interpreted as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, in which, impulsivity, is a result of a hyperdopaminergic state, whereas apathy is viewed as a hypodopaminergic. The study aimed to investigate the presence of impulsiveness and other neuropsychiatric symptoms in Parkinson disease patients with apathy symptoms.Eighty-one patients with Parkinson disease were enrolled in this retrospective study. All subjects were evaluated by the Italian version of the Dimensional Apathy Scale and the Barratt Impulsiveness Scale-version 11, to assess, respectively, apathy and impulsiveness; they were divided into 2 groups (apathy and no apathy). All patients were administered also with questionnaires assessing depressive and anxious symptoms.Statistical analyses showed relevant results. In no-apathy group, education was a significant predictor on impulsiveness (attentional and motor) and apathy (executive and emotional); depression was a significant predictor on planning impulsivity and apathy.This study aimed to consider the importance of apathy and impulsivity in Parkinson disease. Although these are considered as opposite extremes of a spectrum of motivated behavior dependent on dopaminergic dysfunction, these can also occur separately. Moreover, several variables could represent important predictors of apathy and impulsiveness, such as depression. Future investigations should deepen the role of other demographics and psychological variables.     

兔纹状体多巴胺受体的测定及应用

采用~3H-Spiperone作放射性配体,测定了兔纹状体细胞膜多巴胺受体的特异性结合特性,证明特异性结合可达饱和状态,并有两种不同的结合位点。作者用该受体蛋白建立了测定血清中氟哌啶醇的放射受体分析法,最小可测浓度为1.8±0.5ng/ml,批内和批间变异系数分别为6.5%和10.54%。放射受体法测定的结果与高压液相测定的结果密切相关,因前者测定的是血清中游离的氟哌啶醇,后者测定血清中氟哌啶醇的总浓度,故前者测定值低于后者。     

急性胰腺炎血流动力学变化及多巴胺治疗

作者观察了胰管内注射胰蛋白酶和胆汁所致犬急性胰腺炎(AP)时血流动力学变化及多巴胺对 AP 的治疗作用。治疗组在制 AP 模型后10min 开始静脉持续3h 滴注多巴胺,持续3h,每小时0.6mg/kg。AP 组的胰腺血流量(PBF)在制 AP 后迅速下降,全身血流动力学也发生了明显改变。多巴胺治疗可增加 PBF,改善全身血流动力学,降低 AP 犬的死亡率和减轻胰腺炎程度。提示多巴胺可通过改善 AP 早期的胰血供,有效地阻止水肿性胰腺炎向出血坏死性胰腺炎发展。     

Differential Effects of Cocaine on Dopamine Neuron Firing in Awake and Anesthetized Rats

Cocaine (benzoylmethylecgonine), a natural alkaloid, is a powerful psychostimulant and a highly addictive drug. Unfortunately, the relationships between its behavioral and electrophysiological effects are not clear. We investigated the effects of cocaine on the firing of midbrain dopaminergic (DA) neurons, both in anesthetized and awake rats, using pre-implanted multielectrode arrays and a recently developed telemetric recording system. In anesthetized animals, cocaine (10 mg/kg, intraperitoneally) produced a general decrease of the firing rate and bursting of DA neurons, sometimes preceded by a transient increase in both parameters, as previously reported by others. In awake rats, however, injection of cocaine led to a very different pattern of changes in firing. A decrease in firing rate and bursting was observed in only 14% of DA neurons. Most of the other DA neurons underwent increases in firing rate and bursting: these changes were correlated with locomotor activity in 52% of the neurons, but were uncorrelated in 29% of them. Drug concentration measurements indicated that the observed differences between the two conditions did not have a pharmacokinetic origin. Taken together, our results demonstrate that cocaine injection differentially affects the electrical activity of DA neurons in awake and anesthetized states. The observed increases in neuronal activity may in part reflect the cocaine-induced synaptic potentiation found ex vivo in these neurons. Our observations also show that electrophysiological recordings in awake animals can uncover drug effects, which are masked by general anesthesia.     

Dopamine,the Kidney and Essential Hypertension Studies with Gludopa

The formation and action of intrarenal dopamine is reviewed, as also is the evidence for the use of y-L-glutamyl-L-dopa as a relatively renally specific dopaminergic pro-drug. ‘Salt sensitive’ patients with essential hypertension may have a fault in the renal mobilisation of dopamine by sodium chloride. This failure of sodium to dopamine coupling may be particularly prevalent in the Negro race.     

遍地金提取物对大鼠脑纹状体突触体[3H]-多巴胺重摄取抑制试验

目的:评价遍地金提取物对大鼠脑纹状体突触体[3H]-多巴胺重摄取的抑制作用。方法:通过大鼠脑纹状体突触体[3H]-多巴胺重摄取抑制实验,测定其重摄取量cmp及抑制百分率,以评价待试物对多巴胺重摄取的抑制活性。结果:遍地金组平均抑制百分率为65％,IC50=113.25mg·ml-1;St.John's Wort组平均抑制百分率为61％,IC50=28.29mg·ml-1。结论:遍地金提取物与在欧美上市的药物 St.john's Wort均抑制大鼠脑纹状体突触体[3H]-多巴胺重摄取,二者差异无统计学意义。     

Neurons in dopamine-rich areas of the rat medial midbrain predominantly encode the outcome-related rather than behavioural switching properties of conditioned stimuli

Midbrain dopamine neurons are phasically activated by a variety of sensory stimuli. It has been hypothesized that these activations contribute to reward prediction or behavioural switching. To test the latter hypothesis we recorded from 131 single neurons in the ventral tegmental area and retrorubral field of thirsty rats responding during a modified go/no-go task. One-quarter (n = 33) of these neurons responded to conditioned stimuli in the task, which varied according to the outcome with which they were associated (saccharin or quinine solution) and according to whether they triggered a switch in the ongoing sequence of the animal's behaviour ('behavioural switching'). Almost half the neurons (45%) responded differentially to saccharin- vs. quinine-conditioned stimuli; the activity of a minority (15%) correlated with an aspect of behavioural switching (mostly exhibiting changes from baseline activity in the absence of a behavioural switch) and one-third (33%) encoded various outcome-switch combinations. The strongest response was excitation to the saccharin-conditioned stimulus. Additionally, a proportion (38%) of neurons responded during outcome delivery, typically exhibiting inhibition during saccharin consumption. The neurons sampled did not fall into distinct clusters on the basis of their electrophysiological characteristics. However, most neurons that responded to the outcome-related properties of conditioned stimuli had long action potentials (> 1.2 ms), a reported characteristic of dopamine neurons. Moreover, responses to saccharin-conditioned stimuli were functionally akin to dopamine responses found in the macaque and rat nucleus accumbens responses observed within the same task. In conclusion, our data are more consistent with the reward-prediction than the behavioural switching hypothesis.     

Glutamate-induced cell death and formation of radicals can be reduced by lisuride in mesencephalic primary cell culture

Summary. Oxidative stress evoked by excitotoxicity is considered an important factor for the loss of dopaminergic neurons in Parkinson’s disease. In vitro, protective effects of the dopamine agonist lisuride on complex I inhibition in primary dopaminergic cell culture have been reported. However, little is known about the effects of lisuride on glutamate-induced radical formation. Here, effects of lisuride on the formation of nitric oxide (NO) and superoxide radicals following glutamate exposure were studied on primary cell cultures prepared from mouse mesencephala. Glutamate treatment resulted in doubling of NO and superoxide radical formation, increased dopaminergic cell degeneration and extensively altered neuronal appearance. Pretreatment with lisuride significantly lowered the levels of either reactive species and increased the survival of dopaminergic neurons compared to glutamate-treated cultures. Moreover, the beneficial effect of lisuride could be completely inhibited by the D2/D3 receptor antagonist sulpiride when co-treated in cultures.     

Contingent and non-contingent effects of heroin on mu-opioid receptor-containing ventral tegmental area GABA neurons

Opiate activation of mu-opioid receptors (muORs) in the ventral tegmental area (VTA) modulates gamma-aminobutyric acid (GABA) neurotransmission within the mesocorticolimbic dopamine (DA) reward system. We combined in vivo extracellular electrophysiological recordings in anesthetized and freely behaving rats with intracellular Neurobiotin filling and immunocytochemistry to characterize the effects of opiates on VTA GABA neurons, evaluate their discharge activity during opiate self-administration, and identify the cellular sites for opiate activation. We identified a subpopulation of VTA GABA neurons that was characterized by location, spike discharge profile, activation by microelectrophoretic DA, and response to internal capsule (IC) stimulation. Systemic administration of heroin or microelectrophoretic application of the selective muOR agonist [d-Ala2, N-Me-Phe4, Gly-ol]-Enkephalin (DAMGO) reduced VTA GABA neuron firing rate (heroin IC(50) = 0.35 mg/kg) and was blocked by the muOR antagonist naloxone. Heroin also reduced IC-evoked post-stimulus spike discharges, a manifestation of gap-junction-mediated electrical coupling between VTA GABA neurons. The baseline firing rate of VTA GABA neurons significantly increased (239%) following the acquisition of heroin self-administration behavior and transiently increased during each response for heroin (105%), but decreased (49%) following heroin, similar to non-contingent heroin. Electrophysiologically characterized VTA GABA neurons were filled with Neurobiotin and labeled dendrites contained plasmalemmal muOR immunoreactivity. Dually labeled muOR dendrites contained dendrodendritic appositions characteristic of gap junctions. These findings indicate that inhibition of this population of GABAergic neurons by opiates acting on dendritic muORs has implications for modulation of electrical coupling between VTA GABA neurons and dopamine (DA) neurotransmission in the VTA and terminal field regions.     

Cognitive function and social abilities in patients with schizophrenia: relationship with atypical antipsychotics

Although atypical antipsychotics have been associated with improvements in cognitive function in schizophrenia, the neurochemical basis for such effects is not well understood. Candidate neurotransmitter systems primarily involve dopamine and serotonin. The current study explored this issue by examining the cognitive abilities, social function and quality of life in patients with schizophrenia who were medicated with atypical antipsychotics. Comparisons were done for matched schizophrenia patients who were on antipsychotics with (i) an affinity for multiple receptors (olanzapine, clozapine, quetiapine) versus those that have preferential affinity for dopamine receptors (risperidone, amisulpride); and patients on medication with (ii) a high affinity for serotonin (5HT-2A) receptors (risperidone, olanzapine, clozapine) versus those with a low (or no) affinity for 5HT-2A receptors (quetiapine, amisulpride). No differences emerged between groups on any cognitive or social variable when the groups were compared for the dopaminergic properties of antipsychotic medication. By contrast, differences did emerge when patients were compared on the 5HT-2A affinity of their antipsychotic medications. Patients on low 5HT-2A-affinity antipsychotics exhibited a better performance on a measure of selective attention and adjustment to living. These findings accord with the notion that serotonergic mechanisms are important determinants of both the cognitive and the social effects of the atypical antipsychotics.